PERIPHERAL VASODILATING AGENT CONTAINING N-ACYLATED 4-AMINO PIPERIDINE DERIVATIVES AS ACTIVE INGREDIENTS

Abstract: The present invention relates to novel peripheral vasodilating agents characterized by each containing as an active ingredient, a piperidine derivative or pharmaceutically acceptable salt thereof having excellent peripheral vasodilating activity. Said piperidine derivative or pharmaceutically acceptable salt thereof is represented by general formula (1), wherein R, R<1> and R<2> are the same as defined above.

Description: DESCRIPTION PERIPHERAL VASODILATING AGENT CONTAINING N-ACYLATED 4-AMINO PIPERIDINE DERIVATIVES AS ACTIVE INGREDIENTS [Industrial Field of Utilization] The present invention relates to novel peripheral vasodilating agents each containing, as an active ingredient, a piperidine derivative having an excellent peripheral vasodilating activity. [Prior Art and Problems to Be Solved by the Invention] Various compounds having a peripheral vasodil¬ ating activity have been used for the treatment of various disturbances in peripheral circulations. As such compounds, there are known, for example, nicotinic acid derivatives such as Inositol Nicotinate, Ecofrol, Nicametate, Nicotinyl Alcohol Tartarate and the like; norephedrin derivatives such as Nylidrin hydrochloride, Isoxsuprine hydrochloride and the like; Bamethan sulfate and compounds similar thereto; imidazoline derivatives such as Tolazoline hydrochloride and the like; and Trimethylcyclohexyl mandelate. Some of these known peripheral vasodilating compounds, however, have effects to the heart such as effect to heart rate, hypotensive effect, myocardinal contraction effect and the like, and other adverse effects. Therefore, development of new peripheral vasodilating compound is still desired. In addition to the above, various compounds, each of which having chemical structural formula similar to that of the piperidine derivative represented by the below-mentioned general formula (1), have been known in some prior art references for exampl: (A) Prior art references (Patents) filed by the present applicant's company (Otsuka Pharmaceutical Co., Ltd. ) : o U. S. Patent Nos. 4,487,772; 4,454,130; 4,468,402; o U. S. Patent Nos. 4,886,809; 5,071,856 (EP-A-0255134); o Japanese Patent Kokai (Laid-open) No. Sho 57-171974 (1982) [Japanese Patent Publication No. Sho 64-9313 (1989)]; o Japanese Patent Kokai (Laid-open) No. Sho 57-154129 (1982) [Japanese Patent Publication No. Sho 64-53248 (1989)]; o Japanese Patent Kokai (Laid-open) Nos. Sho 54-16478 (1979); o Japanese Patent Kokai (Laid-open) No. Sho 55-85520 (1980); o Japanese Patent Kokai (Laid-open) No. Sho 51-65770 (1976); o Japanese Patent Koaki (Laid-open) No. Sho 51-68574 (1976); o Japanese Patent Kokai (Laid-open) No. Sho 51-118771 ( 1976 ) ; o Japanese Patent Kokai (Laid-open) Nos. Sho 52-282 (1977); and Sho 52-283 (1977); o Japanese Patent Kokai (Laid-open) No. Sho 52-118474 (1977); o U. S. Patent Nos. 4,455,422; 4,567,187; 4,460,593; and 4,619,932; o U. S. Patent No. 5,008,274; (EP-A-0240015) ; o Japanese Patent Kokai (Laid-open) No. Sho 52-83380; o Japanese Patent Kokai (Laid-open) No. Hei 1-61468. (B) Prior art references filed by and/or written by persons who belong to other than the present applicant's company: o J. Org. Chem. 1990, (55), pp. 2552-2554; o Japanese Patent Kokai (Laid-Open) No. Sho 64-79151 [Japanese Patent Koaki (Laid-open) No. Hei 2-169569; EP-A-0296560A2; ϋ. S. Patent Nos. 5,100,901; & 4,895,841)]; o Swiss Patent No. 535,767 [Chem. Abstr., .79., (7): 42395k]; o J. Phar . Sci.,1987, J76., (1), pp. 32-34 [Chem., Abstr., 106. (25): 207384f]; o Japanese Patnet Kokai (Laid-open) No. Sho 59-5610 (EP-A-0097000A2); o Japanese Patent Kokai (Laid-open) No. Hei 1-316356 (EP-A-318029A); o Japanese Patent Kokai (Laid-open) Nos. Sho 63-150237, Sho 63-170311 [Chem, Abstr., 109, (15): 128570x, DE-A-3740383]; o J. Org. Chem., 1984, 49, (15), pp. 2795-2799; o Japanese Patent Kokai (Laid-open) No. Sho 41-19506 [Chem. Abstr., .66., (11): 46341c]; o Japanese Patent Kokai (Laid-open) No. Hei 4-282366 [EP-A-481299, Chem. Abstr., 117, (9): 90151m; EP-A-457686, (Chem. Abstr., 116., (11): 106097r]; o Japanese Patent Kokai (Laid-open) No, Sho 60-226862 [EP-A-156433, Chem. Abstr., 104. (15): 129918a]; o Japanese Patent Kokai (Laid-open) No. Sho 57-192383; Japanese Patent Kokai (Laid-open) Nos. Sho 56-92884; 56-125385; 56-161386; 56-164183; 56-164184, 56-166188, 57-40482; Chem. Pharm. Bull., 1985, 33, (3), pp. 1116-1128; J. Heterocyclic Chem., 20, pp. 565-573 (1983); o Japanese Patent Kokai (Laid-open) No. Sho 60-149583 [EP-A-144101, Chem. Abstr., 104, (9): 68856e]; Japanese Patent Kokai (Laid-open) No. Sho 59-21680 [EP-A-99139, Chem. Abstr., 101, (3): 23473z]; o DE-A-2311570 [Japanese Patent Kokai (Laid-open) No. Sho 49-273] . (C) Prior art reference in which compounds having chemical structural formulae similar to those of piperidine compounds of the present invention, but the former do not overlapped with the latter: o Chem., Abstr., .98. / (7): 53690e [U. S. Patent No. 4,350,634, Japanese Patent Kokai (Laid-open) No., Sho 54-36259]; Chem. Abstr., 91, (7): 56817t [Japanese Patent Kokai (Laid-open) No. Sho 54-8589]; o Chem. Abstr., 107, (13): 115499q [Japanese Patent Kokai (Laid-open) No. Sho 62-89679]: o Chem. Abstr., 114, (11); 101745z [DE-A-3907974] ; o Chem. Abstr., 91, (7): 56817t [Swiss Patent No. 77/8589]; o Chem. Abstr., 100, (9): 68324x [EP-A-90733] ; o Synth. Commun., 1985, 15, (2), pp. 157-163 [Chem. Abstr., 103. (7): 53339u] o EP-A-297661A o Chem. Abstr., 106, (3): 18371p [Japanese Patent Kokai (Laid-open) No. Sho 61-161262]; o Chem. Abstr., 113, (21): 190946k [Japanese Patent Kokai (Laid-open) No. Hei 2-138161]; o Chem. Abstr., 113, (3): 23909u [EP-A-344577] ; Chem. Abstr., 114, (21): 206799y [Japanese Patent Kokai (Laid-open) No. Hei 2-306951]; o Chem. Abstr., 113, (1): 6232a [J. Med. Chem., 1990, 33, (6), pp 1688-1697]; o British Patent No. 2,216,516 o Japanese Patent Koaki (Laid-open) No. Sho 54-92974 [EP-A-1175]; o Japanese Patent Kokai (Laid-open) No. Sho 61-183283 [EP-A-191603] ; o South African Patent No. 6701679 [Japanese Patent Kokai (Laid-open) Nos. Sho 44-17387 & 43-29585] o U. S. Patent No. 3,963,996 o Can. J. Phar . Sci., 16., (1), pp 52-56, 1981 [Chem. Abstr. 95, (19): 162500x]; o Japanese Patent Kokai (Laid-open) No. Sho 62-48665 [DE-A-3529994] o DT-2034640 These compounds being disclosed in the above- mentioned prior art references indeed possess certain pharma-cological activities, for example myocardial contraction increasing activity (positive inotropic activity) , coronary blood flow increasing activity, hypotensive activity and antiinflammatory activity, etc. However, such known compounds do not possess any peripheral vasodilating activities at all. [Means for Solving the Problems] The present inventors made an extensive study in order to develop a peripheral vasodilating agent of new type and, as a result, found that the piperidine derivatives of the general formula (1) shown below or salts thereof have an excellent peripheral vasodilating activity. Each of the piperidine derivatives of the present invention, when contained in and used as a peripheral vasodilating agent, is useful as an agent for improving peripheral circulatory disturbances caused by arterial diseases (e.g. Berger disease, obstructive arteriosclerosis, Raynaud disease and Raynaud syndrome), venous diseases (e.g. venous thrombosis and thrombophle- bites) and other diseases (e.g. congelation, frostbite, feeling of cold and decubitus), and is effective for the preventions and treatments of feeling of coldness accom¬ panied by oversensitivity to the cold and hypnagogic disturbance, etc. The piperidine derivatives of general formula (1) and their salts according to the present invention are characterized particularly in that while they have an excellent peripheral vasodilating activity, they show low pharmacological side-effects to the heart, i.e. a low effect to heart rate, a low hypotensive effect and a low myocardinal contraction effect. The piperidine derivatives contained in the peripheral vasodilating agents of the present invention as an active ingredient are represented by the following general formula (1) . [wherein, R is a group of the formula: /(R 3 ) m (wherein, m is an integer of 1 to 3; R 3 is a hydrogen atom; a nitro group; a lower alkyl group; a halogen atom; a cyano group; a lower alkanoyl group; an aminocarbonyl group which may have 1 to 2 substituents selected from the group consisting of a lower alkyl group and a phenyl group; a lower alkoxy- carbonyl group; a carboxy group; a lower alkoxy group; a hydroxyl group; a hydroxyamino group; a lower alkylthio- lower alkyl group; a lower alkylsulfonyl-lower alkyl group; a hydroxyl group-substituted lower alkyl group; a lower alkenyl group; a lower alkoxycarbonyl group-sub¬ stituted lower alkenyl group; a phenyl group which may have, on the phenyl ring, substituent(s) selected from the group consisting of a hydroxyl group, a phenyl-lower alkoxy group, a lower alkanoyloxy group, a nitro group, an amino group which may have lower alkanoyl group(s) as substituent(s) , a lower alkyl group and a lower alkoxy group; an amino-lower alkoxy group which may have lower alkyl group(s) as substituent(s) ; a morpholinyl group- substituted lower alkoxy group; a 1,2,4-triazolyl group which may have oxo group(s) as substituent(s) on the 1,2,4-triazole ring; a 1,2,3,4-tetrazolyl group; an imidazolyl group which may have 1 to 2 substituents selected from the group consisting of a phenyl group and a lower alkyl group on the imidazole ring; a pyrazolyl group which may have lower alkyl group(s) as substituen- t(s) on the pyrazole ring; a pyridyl group; a pyrrolyl group; a pyrrolydinyl group which may have oxo group(s) as substituent(s) on the pyrrolidine ring; a piperidinyl group which may have oxo group(s) as substituent(s) on the piperidine ring; a benzimididazolyl group; an imida- zolidinyl group which may have oxo group(s) as substitu- ent(s) on the imidazolidine ring; a 2-oxazolinyl group; a 1,2,4-triazolyl-lower alkyl group; a phenoxy group; a phenyl-lower alkoxy group; a lower alkanoyloxy group; a phenyl-lower alkoxycarbonyl group; an amino-lower alkyl group which may have substituent(s) selected from the group consisting of a lower alkyl group and a lower alkanoyl group; or a group of the formula: R -- (wherein, R and R 5 are the same or different and are each a hydrogen atom, a lower alkyl group, a lower alkanoyl group, a lower alkanoyl group having 1 to 3 halogen atoms, a benzoyl group, a pyridylcarbonyl group, a lower alkenylcarbonyl group, an anilinothiocarbonyl group, an aminothiocarbonyl group which may have lower alkyl group(s) as substituent(s) or an aminocarbonyl group which may have 1 to 2 substituents selected from the group consisting of a lower alkyl gorup, a phenyl group and a lower alkenyl group)); a group of the formula: (wherein, X is an oxygen atom or a sulfur atom; R 6 and R 7 are the same or different and are each a hydrogen atom, a lower alkyl group or a phenyl group which may have, on the phenyl ring, substituent(s) selected from the group consisting of a lower alkoxy group, a halogen atom and a nitro group); a lower alkanoyl group which may have hydroxyl group(s) or amino group(s) which may each have lower alkyl group(s) as substituent(s) ; a lower alkanoyl group having 1 to 3 halogen atoms; a lower alkoxycarbonyl group; a pyridylcarbonyl group which may have, on the pyridine ring, substituent(s) selected from the group consisting of a nitro group, an amino group which may have lower alkanoyl group(s) as substituent(s) , a halogen atom, a lower alkyl group, a pyrrolyl group, a lower alkylthio group, a lower alkanoyl group, a hydroxyl group, an aminocarbonyl group which may have lower alkyl group(s) as substituent(s) , a lower alkoxycarobnyl group, a hydroxyl group-substituted lower alkyl group, a phenyl group and a 1,2,4-triazolyl group; a 1,2,4-triazolyl- lower alkanoyl group; a furoyl group which has, on the furan ring, substituent(s) selected from the group consisting of a nitro group, a hydroxyl group- substituted lower alkyl group, a lower alkanoyl group and an amino group which may have lower alkanoyl group(s) as substituent(s); a thienylcarbonyl group which may have, on the thiophene ring, substituent(s) selected from the group consisting of a nitro group, a lower alkyl gorup, a halogen atom and an amino group which may have lower alkanoyl group(s) as substitu¬ ent(s); a fluorenylcarbonyl group which may have, on the fluorene ring, substituent(s) selected from the group consisting of an oxo group and a nitro group; or a group of the formula: (wherein, Z is a group of the formula: -CH 2 - or -NH- or a sulfur atom; Y and W are each a group of the formula: =CH- or a nitrogen atom; the dotted line in the bonding of the fomrula: - is a single bond or a double bond; and the group of the formula: may have 1-4 substituents selected form the group consisting of an oxo group, a lower alkyl group, a lower alkoxy group, a hydroxyl group, a lower alkylthio group, a halogen atom, a nitro group and an amino group)); R 1 is a hydrogen atom or a lower alkyl group which may have hydroxyl group(s) as substituent(s) ; R 2 is a phenyl-lower alkyl group which may have, on the phenyl ring, substituent(s) selected from the group consisting of a lower alkoxy group, a halogen atom, a hdyroxyl group, a nitro group, a lower alkyl group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkoxycarbonyl group, a carbamoyl group, a carboxy group, an amino-lower alkoxy group which may have lower alkyl group(s) as substituent(s), a carboxy group-substituted lower alkoxy group and an amino group which may have substituent(s) selected from the group consisting of a lower alkanoyl group, a lower alkoxy- carbonyl group and aminocarbonyl group(s) which may each have lower alkyl group(s) as substituent(s), which phenyl-lower alkyl group may have lower alkoxycarbonyl group(s) or hydroxyl group-substituted lower alkyl group(s) as substituent(s) in the lower alkyl moiety; a phenoxy-lower alkyl group which may have, on the phenyl ring, substituent(s) selected from the group consisting of a lower alkoxy group, a lower alkyl group, a halogen atom, a nitro group, an amino group which may have lower alkanoyl group(s) as substituent(s) , and a hydroxyl group; a pyridyl-lower alkyl group which may have lower alkyl group(s) as substituent(s) on the pyridine ring; a thienyl-lower alkyl group; a furyl-lower alkyl group; a group of the formula: >27 -B-N R 28 (wherein, B is a lower alkylene group; and R 27 and R 28 are the same or different and are each a hydrogen atom, a lower alkyl group, a phenyl group, a lower alkanoyl group or a benzoyl group); a phthalimido-substituted lower alkyl group, a cycloalkyl-lower alkyl group; a phenyl-lower alkenyl group; a cycloalkyl group which may have phenyl group(s) as substituent(s) ; or a 2,3- dihydro-lH-indenyl group which may have, on the 2,3- dihydro-lH-indene ring, substituent(s) selected from the group consisting of a lower alkoxy group, a hydroxyl group, a nitro group, an amino group which may have lower alkanoyl group(s) as substituent(s); R 1 , R 2 and the nitrogen atom bonded thereto may form a pyrrolidine ring, a piperidine ring, a morpholine ring or a 1,2,3,4-tetrahydroisoquinoline ring, which heterocyclic group may have substituent(s) selected from the group consisting of a hydroxyl group, a lower alkoxy group and a phenyl group; provided that, when is 1 and R 3 is an amino group, R 3 must not be substituted at the 4-positon of the benzoyl group] . Of the compounds of general formula (1) , those having substituents having the following definitions are novel compounds not yet disclosed in any literature. The present invention includes these novel compounds. That is, said novel compounds are those compounds of general formula (1) wherein R is any of the above-mentioned groups, other than an unsubstituted lower alkanoyl group and a lower alkoxycarbnyl group and R 1 and R 2 form, together with the nitrogen atom bonded thereto, a pyrrolidine ring, a piperidine ring or a 1,2,3,4-tetrahydroisoquinoline ring, each having thereon substituent(s) selected from the group consisting of a hydroxyl group, a lower alkoxy group and a phenyl group, or wherein R 3 in R is a group of the formula: -CX-NR 6 R 7 and R 2 is a phenyl-lower alkyl group which may have the above-mentioned substituent(s), a phenoxy-lower alkyl group which may have the above-mentioned substituent(s), or a pyridyl-lower alkyl group which may have the above- mentioned substituent(s) , each lower alkyl moiety of said groups being a C^ alkyl group. Specific examples of the individual groups mentioned with respect to general formula (1) and throughout the present specificaiton are as follows. "Lower alkyl group" includes Cι_ 6 straight- or branched-chain alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, pentyl and hexyl groups and the like. "Halogen atom" includes, for example, a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. "Lower alkanoyl group" inlcudes Cj.g straight- or branched-chain alkanoyl groups such as formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, tert-butylcarbonyl and hexanoyl groups and the like. "Aminocarbonyl group which may have lower alkyl group(s)" can be exemplified by aminocarbonyl groups which may each have C _ 6 straight- or branched- chain alkyl group(s), such as carbamoyl, methylamino- carbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, butylaminocarbonyl, tert- butylaminocarbonyl, pentylaminocarbonyl, hexylamino- carbonyl, dimethylaminocarobnyl, diethylaminocarbonyl, dipropylaminocarbonyl, dibutylaminocarbonyl, dipentyl- aminocarbonyl, dihexylaminocarbonyl, N-methyl-N- ethylaminocarbonyl, N-ethyl-N-propylaminocarbonyl, N- methyl-N-butylaminocarbonyl and N-methyl-N-hexylamino- carbonyl groups and the like. "Lower alkylsulfonyl-lower alkyl group" includes Ci_ 6 straight- or branched-chain alkylsulfonyl group-substituted C ϊ _ 6 straight- or branched-chain alkyl groups such as eth lsulfonylmethyl, 3-ethylsulfonyl- propyl, 4-methylsulfonylbutyl, 2-methylsulfonylethyl, 6- propylsulfonylhexyl, 5-isopropylsulfonylpentyl, 1,1- dimethyl-2-butylsulfonylethyl and 2-methyl-3- methylsulfonylpropyl groups and the like. "Lower alkylthio-lower alkyl group" includes C _ 6 straight- or branched-chain alkylthio group- substituted C^ straight- or branched-chain alkyl groups such as methylthiomethyl, 3-ethylthiopropyl, 4- methylthiobutyl, 2-methylthioethyl, 6-propylthiohexyl, 5-isopropylthiopentyl, 1,1-dimethyl-2-bytylthioethyl and 2-methyl-3-methylthiopropyl groups and the like. "Hydroxyl-substituted lower alkyl group" can be exemplified by C x _ 6 straight- or branched-chain alkyl groups each having 1-3 hydroxyl groups, such as hydroxy¬ methyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, l,l-dimethyl-2- hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl and 2-methyl-3- hydroxypropyl groups and the like. "Lower alkenyl group" includes C 2 . 6 straight- or branched-chain alkenyl groups such as vinyl, allyl, 2-butenyl, 3-butenyl, 1-methylallyl, 2-pentenyl and 2- hexenyl groups and the like. "Lower alkoxycarbonyl-substituted lower alkenyl group" can be exemplified by Cχ_ 6 straight- or branched-chain alkoxycarbonyl-substituted C 2 . 6 straight- or branched-chain alkenyl groups such as 3-methoxy- carbonylallyl, 2-ethoxycarbonylvinyl, 3-isopropoxy- carbonyl-1-methylallyl, 5-butoxycarbonyl-2-pentenyl, 6- pentyloxycarbonyl-2-hexenyl and 4-hexyloxycarbonyl-2- butenyl groups and the like. "Phenyl group which may have, on the phenyl ring, substituent(s) selected from the group consisting of a hydroxyl group, a phenyl-lower alkoxy group, a lower alkanoyloxy group, a nitro group, an amino group which may have lower alkanoyl group(s) as substi- tuent(s), a lower alkyl group and a lower alkoxy group" can be exemplified by phenyl groups which may each have, on the phenyl ring, 1-3 substituents selected from the group consisting of a hydroxyl group, a phenylalkoxy group whose alkoxy moiety is a C x _ 6 straight- or branched-chain alkoxy group, a C x _ 6 straight- or branched-chain alkanoyloxy group, a nitro group, an amino group which may have C x _ 6 straight- or branched- chain alkanoyl group(s) as substituent(s) , a C x _ 6 straight- or branched-chain alkyl group and a C x _ 6 straight- or branched-chain alkoxy group, such as phenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 4- hydroxypheny1, 2,3-dihydroxyphenyl, 2,4-dihydroxyphenyl, 3,4-dihydroxyphenyl, 2,6-dihydroxyphenyl, 3,4,5-trihyd- roxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4- methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4- ethoxypheny1 , 4-isopropoxypheny1 , 4-penty1oxypheny1, 2,4-dimethoxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxy- phenyl, 3-ethoxy-4-methoxyphenyl, 2,3-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,4-dimethoxyphenyl, 2,6-dimethoxy- phenyl, 3,5-dimethoxyphenyl, 3,4-dipentyloxyphenyl, 3,4,5-trimethoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4- ethylphenyl, 2-propylphenyl, 3-propylphenyl, 4- propylphenyl, 2-isopropylphenyl, 3-pentylphenyl, 4- hexylphenyl, 3,4-dimethylphenyl, 3,5-dimethylpheny1, 2,6-dimethylphenyl, 2,3-dimethylphenyl, 2,4-dimethyl- phenyl, 3,4-diethylphenyl, 3,5-diethylphenyl, 3,4,5- trimethylphenyl, 2-methoxy-3-methylphenyl, 2-nitro- phenyl, 3-nitrophenyl, 4-nitrophenyl, 2,4-dinitrophenyl, 2,6-dinitrophenyl, 2,4,6-trinitrophenyl, 4-aminophenyl, 4-propionylaminophenyl, 2-acetylaminophenyl, 3-formyl- aminophenyl, 2-butyrylaminophenyl, 3-isobutyrylamino- phenyl, 4-pentanoylaminophenyl, 4-tert-butylcarbonyl- aminopheny1, 3-hexanoylaminophenyl, 3,4-diaminopheny1, 3,4,5-triaminophenyl, 3,4-diacetylaminopheny1 , 4- acetyloxyphenyl , 3,4-dibenzyloxyhenyl, 2,4-diacetyl- oxyphenyl, 4-benzyloxyphenyl, 3-propionyloxyphenyl, 2- butyrylphenyl, 4-pentanoyloxyphenyl, 4-hexanoyloxy- phenyl, 4-(2-phenylethoxy)phenyl, 3-(3-phenylpropoxy)- pheny1, 4-(4-phenylbutoxy)phenyl, 2-(5-phenyl- pentyloxy)phenyl and 4-(6-phenylhexyloxy)phenyl groups and the like. "Amino-lower alkoxy group which may have lower alkyl group(s) as substituent(s) " can be exemplified by amino-substituted C x _ 6 straight- or branched-chain alkoxy groups which may each have one to two C x _ 6 straight- or branched-chain alkyl groups as substituent(s) , such as aminomethoxy, 1-aminoethoxy, 2-aminoethoxy, 3- aminopropoxy, 4-aminobutoxy, 5-aminopentyloxy, 6- aminohexyloxy, 1,1-dimethyl-2-aminoethoxy, 2-methyl-3- aminopropoxy, methylaminomethoxy, ethylaminomethoxy, propylaminomethoxy, isopropylaminomethoxy, butylamino- methoxy, tert-butylaminomethoxy, pentylaminomethoxy, hexylaminomethoxy, dimethylaminomethoxy, diethyl- aminomethoxy, dipropylaminomethoxy, dibutylaminomethoxy, dipentylaminomethoxy, dihexylaminomethoxy, N-methyl-N- ethylaminomethoxy, N-methyl-N-propylaminomethoxy, N- methyl-N-butylaminometoxy, N-methyl-N-hexylaminomethoxy, 1-methylaminoethoxy, 2-ethylaminoetoxy, 3-propylamino- propoxy, 4-butylaminobutoxy, l,l-dimethyl-2-pentylamino- ethoxy, 5-hexylaminopentyloxy, 6-dimethylaminohexyloxy, 2-diethylaminoethoxy, 1-(N-methyl-N-hexylamino)ethoxy, 3-dihexylaminopropoxy, 4-dibutylaminobutoxy and 2-(N- methyl-N-pentylamino)ethoxy groups and the like. "Morpholinyl-substituted lower alkoxy group" includes morpholinyl-substituted alkoxy groups whose alkoxy moieties are each a C x _ 6 straight- or branched- chain alkoxy group, such as morpholinomethoxy, 2- morpholinoethoxy, l-(2-morpholinyl)ethoxy, 3-(3- morpholinyl)propoxy, 4-morpholinobutoxy, 5-(2- morpholinyl)pentyloxy and 6-(3-morpholinyl)hexyloxy groups and the like. "1,2,4-Triazolyl group which may have oxo group(s) as substituent(s) on the 1,2,4-triazole ring" includes 1,2,4-triazolyl, 3-oxo-l,2,4-triazolyl, 5-oxo- 1,2,4-triazolyl, etc. "Imidazolyl group which may have, on the imidazole ring, 1-2 substituents selected from the group consisting of a phenyl group and a lower alkyl group" includes imidazolyl groups which may each have, on the imidazole ring, 1-2 substituents selected from the group consisting of a phenyl group and a C x _ 6 straight- or branched-chain alkyl group, such as imidazolyl, 4- phenylimidazolyl, 2-ethylimidazolyl, 2-ethyl-4- methylimidazolyl, 2-methyl-4-phenylimidazolyl, 2- propylimidazolyl, 4-butylimidazolyl, 4-pentylimidazolyl, 2-hexylimidazolyl and 2-phenylimidazolyl groups and the like. "Pyrazolyl group which may have lower alkyl group(s) on the pyrazole ring" can be exemplified by pyrazolyl groups which may each have, on the pyrazole ring, C _ 6 straight- or branched-chain alkyl group(s), such as pyrazolyl, 3-methylpyrazolyl, 4-ethylpyrazolyl, 1-methylpyrazolyl, 3-propylpyrazolyl, 4-butylpyrazolyl, 3-pentylpyrazolyl and 4-hexylpyrazolyl groups and the like. "Pyrrolidinyl group which may have oxo group(s) as substituent(s) on the pyrrolidine ring" includes pyrrolidinyl, 2-oxopyrrolidinyl, 3- oxopyrrolidinyl, etc. "Piperidinyl group which may have oxo group(s) as substituent(s) on the piperidine ring" includes piperidinyl, 2-oxopiperidinyl, 3-oxopiperidinyl, 4- oxopiperidinyl, etc. "Imidazolidinyl group which may have oxo group(s) as substituent(s) on the imidazolidine ring" includes imidazolidinyl, 2-oxoimidazolidinyl, 4- oxoimidazolidinyl, 5-oxoimidazolidinyl, etc. "1,2,4-Triazolyl-lower alkyl group" can be exemplified by 1,2,4-triazolylalkyl groups whose alkyl moieties are each a C x _ 6 straight- or straight-chained alkyl group", such as (l,2,4-triazol-l-yl)methyl, 2- (1,2,4-triazol-3-yl)ethyl, 1-(1,2,4-triazol-5-yl)ethyl, 3-(l,2,4-triazol-l-yl)propyl, 4-( (l,2,4-triazol-3- yl)butyl, 5-(l,2,4-triazol-5-yl)pentyl, 6-(1,2,4- triazol-1-yl)hexyl, 1,l-dimethyl-2-(1,2,4-triazol-l- yl)ethyl and 2-methyl-3-(l,2,4-triazol-l-yl)propyl groups and the like. "Lower alkenylcarbonyl group" includes C 2 . 6 straight- or branched-chain alkenylcarbonyl groups such as vinylcarbonyl, allylcarbonyl, 2-butenylcarbonyl, 3- butenylcarbonyl, 1-methylallylcarbonyl, 2-pentenyl- carbonyl and 2-hexenylcarbonyl groups and the like. "Aminothiocarbonyl group which may have lower alkyl group(s) as substituent(s) " can be exemplified by aminothiocarbonyl groups which may each have C x _ 6 straight- or branched-chain alkyl group(s) as substi¬ tuent(s), such as aminothiocarbonyl, methylaminothio- carbonyl, ethylaminothiocarbonyl, propylaminothio- carbonyl, isopropylaminothiocarbonyl, butylaminothio- carbonyl, tert-butylaminothiocarbonyl, pentylaminothio- carbonyl, hexylaminothiocarbonyl, dimethylaminothio- carbonyl, diethylaminothiocarbonyl, dipropylaminothio- carbonyl, dibutylaminothiocarbonyl, dipentylamino- thiocarbonyl , dihexylaminothiocarbonyl , N-methyl-N- ethyla inothiocarbonyl, N-ethyl-N-propylaminothio- carbonyl, N-methyl-N-butylaminothiocarbonyl and N- methyl-N-hexylaminothiocarbonyl groups and the like. "Aminocarbonyl group which may have 1-2 substituents selected from the group consisting of a lower alkyl group, a phenyl group and a lower alkenyl group" can be exemplified by aminocarbonyl groups which may each have 1-2 substituents selected from the group consisting of a C x _ 6 striaght- or branched-chain alkyl group, a phenyl group and a C 2 . 6 straight- or branched- chain alkenyl group, such as aminocarbonyl, phenylamino- carbonyl , diphenylaminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl , isopropyl- aminocarbonyl, butylaminocarbonyl, tertbutylamino- carbonyl, pentylaminocarbonyl, hexylaminocarbonyl, dimethylaminocarbonyl , diethylaminocarbonyl , dipropyl¬ aminocarbonyl , dibutylaminocarbonyl , dipentylamino- carbonyl, dihexylaminocarbonyl, N-methyl-N-ethylamino- carbonyl, N-ethyl-N-propylaminocarbonyl, N-methyl-N- butylaminocarbonyl, N-methyl-N-hexylamnocarbonyl, N- methyl-N-phenylaminocarbonyl, N-ethyl-N-phenylamino- carbonyl, vinylaminocarbonyl, allylaminocarbonyl, (2- butenyl)aminocarbonyl, (3-butenyl)aminocarbonyl , (1- methylallyl)aminocarbonyl, (2-pentenyl)aminocarbonyl, (2-hexenyl)aminocarbonyl, N-methyl-N-allylaminocarbonyl and diallylaminocarbonyl groups and the like. "Phenyl group which may have, on the phenyl ring, substituent(s) selected from the group consisitng of a lower alkoxy group, a halogen atom and a nitro groups" can be exemplified by phenyl groups which may each have, on the phenyl ring, 1-3 substituents selected from the group consisting of a C^ straight- or branched-chain alkoxy group, a halogen atom and a nitro group, such as phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4- ethoxyphenyl , 4-isopropoxyphenyl, 4-pentyloxyphenyl, 2 ,4-dimethoxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxy- phenyl, 3-ethoxy-4-methoxyphenyl, 2,3-dimethoxyphenyl, 3,4-diethoxypheny1, 2,5-dimethoxyphenyl, 2,6-dimeth¬ oxyphenyl, 3,5-dimethoxyphenyl, 3,4-dipentyloxyphenyl, 3,4,5-trimethoxyphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4- fluorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromo- phenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 3,4- dichlorophenyl, 3,5-dichlorophenyl, 2,6-dichlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 3,4-difluoro¬ phenyl, 3,5-dibromophenyl, 3,4,5-trichlorophenyl, 2- methoxy-3-chlorophenyl, 2-nitrophenyl, 3-nitrophenyl, 4- nitrophenyl, 2,4-dinitrophenyl, 2,6-dinitrophenyl and 2,4,6-trinitrophenyl groups and the like. "Amino group which may have lower alkyl group(s)" can be exemplified by amino groups which may each have one to two C x _ 6 straight- or branched-chain alkyl groups as substituent(s) , such as amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutyl- amino, dipentylamino, dihexylamino, N-methyl-N-ethyl- amino, N-ethyl-N-propylamino, N-methyl-N-butylamino and N-methyl-N-hexylamino groups and the like. "Lower alkanoyl group which may have, as substituent(s) , hydroxyl group(s) or amino group(s) which may each have lower alkyl group(s)" can be exemplified by the above-mentioned alkanoyl groups and also by C 2 _ 6 straight- or branched-chain alkanoyl groups which may each have, as substituent(s), hydroxyl group(s) or amino group(s) which may each have one to two Cj_ 6 straight- or branched-chain alkyl groups, such as 2-hydroxyacetyl, 3-hydroxypropionyl, 2-hydroxy- propionyl, 4-hydroxybutyryl, 2,2-dimethyl-3-hydroxy- propionyl, 5-hydroxypentanoyl, 6-hydroxyhexanoyl, 3- methyl-4-hydroxybutyryl, 2-aminoacetyl, 4-aminobutyryl, 4-methylaminobutyryl, 2-dimethylaminoacetyl, 2-methyl- aminoacetyl, 4-dimethylaminoacetyl, 3-ethylamino- propionyl, 2-isopropylaminopropionyl, 2,2-dimethyl-3- butylaminopropionyl, 5-pentylaminopentanoyl, 6-hexyl- aminohexanoyl, 3-methyl-4-(N-methyl-N-ethylamino)butyryl groups and the like. Incidentally, "lower alkanoyl group having, as substituent, hydroxyl group(s) or amino group(s) which may each have lower alkyl group(s)" includes the above-mentioned groups other than unsubsti- tuted lower alkanoyl groups. "Lower alkanoyl group having 1-3 halogen atoms" includes C^ straight- or branched-chain alkanoyl groups each having 1-3 halogen atoms, such as 2,2,2- trifluoroacetyl, 2,2,2-trichloroacetyl, 2-chloroacetyl, 2-bromoacetyl, 2-fluoroacetyl, 2-iodoacetyl, 2,2- difluoroacetyl, 2,2-dibromoacetyl, 3,3,3-trifluoro- propionyl, 3,3,3-trichloropropionyl, 3-chloropropionyl, 2,3-dichloropropionyl, 4,4,4-trichlorobutyryl, 4- fluorobutyryl, 5-chloropentanoyl, 3-chloro-2-methyl- propionyl, 6-bromohexanoyl and 5,6-dibromohexanoyl groups and the like. "Lower alkoxycarbonyl group" can be exempli¬ fied by Cj.g straight- or branched-chain alkoxycarbonyl groups such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl and hexyloxy- carbonyl groups and the like. "Amino group which may have lower alkanoyl group(s)" can be exemplified by amino groups which may each have C x _ 6 straight- or branched-chain alkanoyl group(s), such as amino, formylamino, acetylamino, propionylamino, butyrylamino, isobutyrylamino, pentanoylamino, tert-butvlcarbonvlamino and hexanoyl- amino groups and the like. "Pyridylcarbonyl group which may have, on the pyridine ring, substituent(s) selected from the group consisting of a nitro group, an amino group which may have lower alkanoyl group(s) as substituent(s) , a halogen atom, a lower alkyl group, a pyrrolyl group, a lower alkylthio group, a lower alkanoyl group, a hydroxyl group, an aminocarbonyl group which may have lower alkyl group(s) as substituent(s) , lower alkoxy- carbonyl group(s), hydroxyl-substituted lower alkyl group(s), phenyl group(s) and 1,2,4-triazolyl group(s)" can be exemplified by pyridylcarbonyl groups which may each have, on the pyridine ring, 1-3 substituents selected from the group consisting of a nitro group, an amino group which may have C^e straight- or branched- chain alkanoyl group(s) as substituent(s) , halogen atom(s), C x _ 6 straight- or branched-chain alkyl group(s), pyrrolyl group(s), C x _ 6 straight- or branched-chain alkylthio group(s), C x _ 6 straight- or branched-chain alkanoyl group(s), hydroxyl group(s), aminocarbonyl group(s) which may each have C x _ 6 straight- or branched- chain alkyl group(s) as substituent(s) , C x _ 6 straight- or branched-chain alkoxycarbonyl group(s), C x _ 6 straight- or branched-chain alkyl group(s) each having 1-3 hydroxyl groups, phenyl group(s) and 1,2,4-triazolyl group(s) , such as pyridylcarbonyl, 2-nitropyridylcarbonyl, 3- nitropyridylcarbonyl, 4-nitropyridylcarbonyl, 2- aminopyridylcarbonyl, 3-aminopyridylcarbonyl, 4-amino- pyridylcarbonyl, 2-propionylaminopyridylcarbonyl, 3- acetylaminopyridylcarbonyl, 4-butyrylaminopyridyl- carbonyl, 2-pentanoylaminopyridylcarbonyl, 3- hexanoylaminopyridylcarbonyl, 2-chloropyridylcarbonyl, 3-bromopyridylcarbonyl, 4-fluoropyridylcarbonyl, 2- iodopyridylcarbonyl, 2,4-dichloropyridylcarbonyl, 2- methyllpyridylcarbonyl, 3-ethylpyridylcarbonyl, 4- propylpyridylcarbonyl, 2-butylpyridylcarbonyl, 3- pentylpyridylcarbonyl, 4-hexylpyridylcarbonyl, 2,4- dimethylpyridylcarbonyl, 2,4,6-trimethylpyridylcarbonyl, 2-(1-pyrrolyl) yridylcarbonyl, 2-amino-3-methylpyridyl- carbonyl, 2-propionylaminopyridylcarbonyl, 2-(l-l,2,4- triazol-1-yl)pyridylcarbonyl, 2-methylthiopyridyl- carbonyl, 3-ethylthiopyridylcarbonyl, 4-propylthio- pyridylcarbonyl, 2-butylthiopyridylcarbonyl, 3- pentylthiopyridylcarbonyl, 4-hexylthiopyridylcarbonyl, 2-acetylpyridylcarbonyl, 2-acetyl-4-methylpyridyl- carbonyl, 3-propionylpyridylcarbonyl, 4-butyl- pyridylcarbonyl, 2-formylpyridylcarbonyl, 3-pentanoyl- pyridylcarbonyl, 4-hexanoylpyridylcarbonyl, 2-hydroxy- pyridylcarbonyl, 3-hydroxypyridylcarbonyl, 4-hydroxy- pyridylcarbonyl, 2,4-dihydroxypyridylcarbonyl, 2,4,6- trihydroxypyridylcarbonyl, 2-hydroxy-3-chloropyridyl- carbonyl, 2-ethylaminocarbonylpyridylcarbonyl, 3- methylaminocarbonylpyridylcarbonyl, 4-propylamino- carbonylpyridylcarbonyl, 2-butylaminocarbonylpyridyl- carbonyl, 3-pentylaminocarbonylpyridylcarbonyl, 4- hexylaminocarbonylpyridylcarbonyl, 2-carbamoylpyridyl- carbonyl, 2-dimethylaminocarbonylpyridylcarbonyl, 2- methoxycarbonylpyridylcarbonyl, 3-ethoxycarbonyl- pyridylcarbonyl, 4-propoxycarbonylpyridylcarbonyl, 2- butoxycarbonylpyridylcarbonyl, 3-pentyloxycarbonyl- pyridylcarbonyl, 4-hexyloxycarbonylpyridylcarbonyl, 2- hydroxymethylpyridylcarbonyl , 2 ,4-dimethyl-3- propionylaminopyridylcarbonyl, 3-propionylamino-4- methylpyridylcarbonyl, 3-(2-hydroxyethyl)pyridyl¬ carbonyl, 4-(3-hydroxypropyl)pyridylcarbonyl, 2-(4- hydroxybutyl)pyridylcarbonyl, 3-(5-hydroxypentyl)- pyridylcarbonyl, 4-(6-hydroxyhexyl)pyridylcarbonyl, 2- (2,3-dihydroxypropyl)pyridylcarbonyl, 4-(5,5,4- trihydroxybutyl)pyridylcarbonyl, 2-phenylpyridylcarbonyl and 3-phenylpyridylcarbonyl groups and the like. "1,2,4-Triazolyl-lower alkanoyl group" can be exemplified by 1,2,4-triazolylalkanoyl groups whose alkanoyl moieties are each a C 2 . 6 straight- or branched- chain alkanoyl group, such as 2-(1,2,4-triazol-l- yl)acetyl, 3-(l,2,4-triazol-3-yl)propionyl, 2-(1,2,4- triazol-5-yl)propionyl, 4-(l,2,4-triazol-l-yl)butyryl, 2,2-dimethyl-3-(1,2,4-triazol-l-yl)propionyl, 5-(1 , 2 ,4- triazol-3-yl)pentanoyl , 6-(1 , 2 ,4-triazol-5-yl)hexanoyl and 3-methyl-4-(l,2,4-triazol-l-yl)butyryl groups and the like. "Lower alkyl group which may have hydroxyl group(s) as substituent(s) " can be exemplified by (a) the above-mentioned lower alkyl groups and (b) C x _ 6 straight- or branched-chain alkyl groups each having 1-3 hydroxyl groups, obtained by introducing said hydroxyl group(s) into the lower alkyl group (a). "Lower alkylthio group" can be exemplified by Cj.g straight- or branched-chain alkylthio groups such as methylthio, ethylthio, propylthio, isopropylthio, butylthio, tert-butylthio, pentylthio and hexylthio groups and the like. "Lower alkylsulfinyl group" can be exemplified by C x _ 6 straight- or branched-chain alkylsulfinyl groups such as methylsulfinyl, ethylsulfinyl, isopropyl- sulfinyl, butylsulfinyl, tert-butylsulfinyl, pentyl- sulfinyl, hexylsulfinyl groups and the like. "Carboxy-substituted lower alkoxy group" includes carboxyalkoxy groups whose alkoxy moities are each a C x _ 6 straight- or branched-chain alkoxy group, such as carboxymethoxy, 2-carboxyethoxy, 1-carboxy- ethoxy, 3-carboxypropoxy, 4-carboxybutoxy, 5- carboxypentyloxy, 6-carboxyhexyloxy, 1,l-dimethyl-2- carboxyethoxy and 2-methyl-3-carboxypropoxy groups and the like. "Amino group which may have, as substi¬ tuent(s), lower alkanoyl group(s), lower alkoxycarbonyl group(s), or amincalbonyl group(s) which may each have lower alkyl group(s)" can be exemplified by amino groups which may have, as substituent(s), C x _ 6 straight- or branched-chain alkanoyl group(s), C x _ 6 straight- or branched-chain alkoxycarbonyl group(s), or aminocarbonyl group(s) which may each have C x _ 6 straight- or branched- chain alkyl group(s), such as amino, carbamoylamino, methylaminocarbonylamino, ethylaminocarbonylamino, propylaminocarbonylamino, isopropylaminocarbonylamino, butylaminocarbonylamino, tert-butylaminocarbonylamino, pentylaminocarbonylamino, hexylaminocarbonylamino, dimethylaminocarbonylamino, diethylaminocarbonylamino, dipropylaminocarbonyla ino, dibutylaminocarbonylamiono, dipentylaminocarbonylamino, dihexylaminocarbonylamino, N-acetyl-N-ethylaminocarbonylamino, N-propionyl-N- propylaminocarbonylamino, N-methoxycarbonyl-N-butyl- aminocarbonylamino, N-ethoxycarbonyl-N-hexylamino- carbonylamino, formylamino, acetylamino, propionylamino, butyrylamino, isobutyrylamino, pentanoylamino, tert- butylcarbonylamino, hexanoylamino, methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino, iso- propoxycarbonylamino, butoxycarbonylamino, tert-butoxy- carbonylamino, pentyloxycarbonylamino and hexyloxy- carbonylamino groups and the like. "Phenoxy-lower alkyl group which may have, on the phenyl ring, substituent(s) selected from the group consisting of a lower alkoxy group, a lower alkyl group, a halogen atom, a nitro group, a hydroxyl group and a amino group which may have lower alkanoyl group(s)" can be exemplified by phenoxyalkyl groups which may each have, on the phenyl ring, 1-3 substituents selected from the group consisting of a C x _ 6 straight- or branched- chain alkoxy group, a C x _ 6 straight- or branched-chain alkyl group, a halogen atom, a nitro group, a hydroxyl group and an amino group which may have C x _ 6 straight- or branched-chain alkanoyl group(s), and whose alkyl moieties are each a C x _ 6 straight- or branched-chain alkyl group, such as phenoxymethyl, 2-phenoxyethyl, 1- phenoxyethyl, 3-phenoxypropyl, 4-phenoxybutyl, 5- phenoxypenty1, 6-phenoxyhexy1, 1,1-dimethyl-2- phenoxyethyl, 2-methyl-3-phenoxypropyl, (2-hydroxy- phenoxy)methyl, 2-(4-hydroxyphenoxy)ethyl, l-(3-hydroxy- phenoxy)ethyl, 3-(2-hydroxyphenoxy)propyl, 4-(3-hydroxy- phenoxy)butyl, 5-(4-hydroxyphenoxy)pentyl, 6-(2-hydroxy- phenoxy)hexyl , (2-methoxyphenoxy)methyl , 2-(4-methoxy- phenoxy)ethyl , l-(3-ethoxyphenoxy)ethyl, 3-(2-propoxy- phenoxy)propyl, 4-(3-butoxyphenoxy)butyl, 5-(4- pentyloxyphenoxy)pentyl, 6-(2-hexyloxyphenoxy)hexyl, l,l-dimethyl-2-(2,4-dimethoxyphenoxy)ethyl, 2-methyl-3- (3,4,5-trimethoxyphenoxy)propyl, (2,3-dihydroxy- phenoxy)methyl, (3,4,5-trihydroxyphenoxy)methyl, 2-(3,4- dimethoxyphenoxy)ethyl, 2-(3-methoxy-4-hydroxyphenoxy)- ethyl, (2-methylphenoxy) ethyl , 2-(4-methylphenoxy)- ethyl, 2-(3-methylphenoxy)ethyl, l-(4-methylphenoxy)- ethyl, 3-(2-ethylphenoxy)propyl, 4-(3-ethylphenoxy)- butyl, l,l-dimethyl-2-(4-ethylphenoxy)ethyl, 5-(4- isopropylphenoxy)pentyl, 6-(4-hexylphenoxy)hexyl, (3,4- dimethylphenoxy)methyl , (3,4,5-trimethylphenoxy)methyl, (2,5-dimethylphenoxy)methyl, (2-chlorophenoxy)methyl, (4-chlorophenoxy)methyl, (3-chlorophenoxy)methyl, 2-(3- chlorophenoxy)ethyl, (2-fluorophenoxy)methyl, l-(4- chlorophenoxy)ethyl, 3-(2-fluorophenoxy)propyl, 4-(3- fluorophenoxy) tyl, 5-(4-fluorophenoxy)pentyl, 1,1- dimethy1-2-(2-bromophenoxy)ethyl, 6-(3-bromophenoxy)- hexyl, (4-bromophenoxy)methyl, 2-(2-iodophenoxy)ethyl, l-(3-iodophenoxy)ethyl, 3-(4-iodophenoxy)propyl, (3,4- dichlorophenoxy)methyl, (3,5-dichlorophenoxy)methyl, (2 ,6-dichlorophenoxy)methyl , (2 ,3-dichlorophenoxy)- methyl, (2,4-dichlorophenoxy)methyl, (3,4-difluoro- phenoxy) ethyl, (3,5-dibromophenoxy)methyl, (3,4,5-tri- chlorophenoxy)methyl, (2-methoxy-3-chlorophenoxy)methyl, (2-nitrophenoxy)methyl, 2-(3-nitrophenoxy)ethyl, 2-(4- nitrophenoxy)ethyl, l-(2-nitrophenoxy)ethyl, 3-(3- nitrophenoxy)propyl, 4-(4-nitrophenoxy)butyl, 5-(2- nitrophenoxy)pentyl , 2-(3-methyl-4-nitrophenoxy)ethyl , 2-(3-methyl-4-aminophenoxy)ethyl, 6-(3-nitrophenoxy)- hexyl, 2-(3,4-dinitrophenoxy)ethyl, 2-(3,4,5- trinitrophenoxy)ethyl, (2-aminophenoxy)methyl, 2-(3- aminophenoxy)ethyl, 2-(4-aminophenoxy)ethyl, l-(2- aminophenoxy)ethyl, 3-(3-aminophenoxy)propyl, 4-(4- aminophenoxy)butyl, 5-(2-aminophenoxy)pentyl, 6-(3- aminophenoxy)hexyl, 2-(3,4-diaminophenoxy)ethyl, 2- (3,4,5-1riaminophenoxy)ethyl, (2-propionylaminophenoxy)- ethyl, 3-(3-butyrylaminophenoxy)propyl, 4-(4-pentanoyl- aminophenoxy)butyl , 5-(5-hexanoylaminophenoxy)pentyl, 2- (4-acetylaminophenoxy)ethyl and 6-(2-acetylamino- phenoxy)hexyl groups and the like. "Pyridyl-lower alkyl group which may have lower alkyl group(s) as substituent(s) on the pyridine ring" can be exemplified by pyridylalkyl groups which may each have, on the pyridine ring, one to three C x _ 6 straight- or branched-chain alkyl groups and whose alkyl moieties are each a C x _ 6 straight- or branched-chain alkyl group, such as (2-pyridyl)methyl, 2-(2- pyridyl)ethyl, 2-(3-pyridyl)ethyl, l-(4-pyridyl)ethyl, 3-(2-pyridyl)propyl, 4-(3-pyridyl)butyl, 5-(4- pyridyl)pentyl, 6-(2-pyridyl)hexyl, l,l-dimethyl-2-(3- pyridyl)ethyl, 2-methyl-3-(4-pyridyl propyl, (4-methy1- 2-pyridyl)methyl, 2-(2-methyl-6-pyridyl)ethyl, l-(3- propyl-4-pyridyl)ethyl, 3-(4-butyl-2-pyridyl)propyl, 4- (2-pentyl-3-pyridyl)butyl, 5-(3-hexyl-4-pyridyl)pentyl, 6-(3 ,4-dimethyl-2-pyridyl)hexyl , 1,1-dimethyl-2-(2,4,6- trimethyl-3-pyridyl)ethyl and 2-methyl-3-(2,3-dimethyl- 4-pyridyl)propyl groups and the like. "Phenyl-lower alkyl group which may have, on the phenyl ring, substituent(s) selected from the group consisting of a lower alkoxy group, a halogen atom, a hydroxyl group, a nitro group, a lower alkyl group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkoxycarbonyl group, a carbamoyl group, a carboxy group, an amino-lower alkoxy group which may have lower alkyl group(s) as substituent(s) , a carboxy-lower alkoxy group and an amino group which may have lower alkanoyl group(s), lower alkoxycarbonyl group(s) or aminocarbonyl group(s) which may each have lower alkyl group(s), and whose lower alkyl moiety may have, as substituent(s) , lower alkoxycarbonyl group(s) or hydroxyl-substituted lower alkyl group(s)" can be exemplified by phenylalkyl groups whose alkyl moieties are each a C x _ 6 straight- or branched-chain alkyl group, which may each have, on the phenyl ring, 1-3 substituents selected from the group consisting of a C x _ 6 straight- or branched-chain alkoxy group, a hydroxyl group, a nitro group, a C^ straight- or branched-chain alkyl group, a halogen atom, a C x _ 6 straight- or branched-chain alkylthio group, a C^ straight- or branched-chain alkylsulfinyl group, a C x _ 6 straight- or branched-chain alkoxycarbonyl group, a carbamoyl group, a carboxy group, an amino-substituted C _ 6 straight- or branched-chain alkoxy group which may have one to two C^ straight- or branched-chain alkyl groups as substituent(s), a carboxyalkoxy group whose alkoxy moiety is a C x _ 6 straight- or branched-chain alkoxy group, and an amino group which may have, as substituent(s) , C x _ 6 straight- or branched-chain alkanoyl group(s), C x _ 6 straight- or branched-chain alkoxycarbonyl group(s) or aminocarbonyl group(s) which may each have Ci. 6 straight- or branched-chain alkyl group(s) as subst- ituent(s), and whose alkyl moieties may each have, as substituent(s) , C x _ 6 straight- or branched-chain alkoxy¬ carbonyl group(s) or C x _ 6 straight- or branched-chain alkyl group(s) each having 1-3 hydroxyl groups, such as benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 2- phenylpropyl, 4-phenylbutyl, l,l-dimethyl-2-phenylethyl, 5-phenylpentyl, 6-phenylhexyl, 2-methyl-3-phenylpropyl, l-methoxycarbonyl-2-phenylethyl , l-hydroxymethyl-2- phenylethyl, 1-ethoxycarbonyl-3-phenylpropyl, l-(2- hydroxyethyl)-4-phenylpropyl, 1-hydroxymethyl-2-(4- methoxyphenyl)ethyl, 2-(4-methoxyphenyl)ethyl, 2-(3- methoxyphenyl)ethyl, 1-(4-methoxyphenyl)ethyl , 2 - methoxybenzyl, 3-(2-ethoxyphenyl)propyl, 4-(3-ethoxy- phenyl)butyl, 1,1-dimethyl-2-(4-ethoxyphenyl)ethyl, 5- (4-isopropoxyphenyl)pentyl, 6-(4-hexyloxyphenyl)hexyl, 3,4-dimethoxybenzyl, 3,4,5-trimethoxybenzyl, 2,5- dimethylbenzyl, 3-methoxybenzyl, 4-methoxybenzyl, 2,4- diethoxybenzyl, 2,3-dimethoxybenzyl, 2,4-dimethoxy- benzyl, 2,6-dimethoxybenzyl, 4-ethylthiobenzyl, 2-(4- methylthiophenyl)ethyl, l-(2-propylthiophenyl)ethyl, 3- (2-buytlthiophenyl) propyl, 4-(3-pentylthiophenyl)butyl, 1,l-dimethyl-2-(4-hexylthiophenyl)ethyl, 5-(2-methyl- thiophenyl)pentyl, 6-(methylthiophenyl)hexyl, 2-hydroxy- benzyl, 4-hydroxybenzyl, 2-(3-hydroxyphenyl)ethyl, l-(4- hydroxypheny1)ethyl, 2-(4-hydroxypheny1)ethyl, 2-(2- hydroxypheny1)ethyl, 3-(2-hydroxypheny1)propyl, 4-(3- hydroxypheny1)butyl, 5-(2-hydroxypheny1)pentyl, 6-(3- hydroxyphenyl)hexyl, 3,4-dihydroxybenzyl, 3,4,5- trihydroxybenzyl, 2-methylbenzyl, 2-(4-methylphenyl)- ethyl, 2-(3-methylphenyl)ethyl, 1-(4-methylphenyl)ethyl, 3-(2-ethylphenyl)propyl, 4-(3-ethylphenyl)butyl, 1,1- dimethyl-2-(4-ethylphenyl)ethyl, 5-(4-isopropylphenyl)- pentyl, 6-(4-hexylphenyl)hexyl, 3,4-dimethylbenzyl, 3,4,5-trimethyl benzyl, 2,5-dimethylbenzyl, 2-chloro- benzyl, 4-chloro benzyl, 3-chlorobenzyl, 2-(3-chloro- phenyl)ethyl, 2-fluorobenzyl, l-(4-chlorophenyl)ethyl, 3-(2-fluoro phenyl)propyl, 4-(3-fluorophenyl)butyl, 5- (4-fluorophenyl)pentyl, 1,1-dimethyl-2-(2-bromophenyl)- ethyl, 6-(3-bromophenyl)hexyl, 4-bromobenzyl, 2-(2- iodophenyl) ethyl, l-(3-iodphenyl)ethyl, 3-(4-iodo- phenyl)propyl, 3,4-dichlorobenzyl, 3,5-dichlorobenzyl, 2,6-dichlorobenzyl, 2,3-dichlorobenzyl, 2,4-dichloro- benzyl, 3,4-difluorobenzyl, 3,5-dibromobenzyl, 3,4,5- trichlorobenzyl, 2-methoxy-3-chlorobenzyl, 2-nitro- benzyl, 2-(3-nitrophenyl)ethyl, 2-(4-nitrophenyl)ethyl, l-(2-nitrophenyl)ethyl, 3-(3-nitrophenyl)propyl, 4-(4- nitrophenyl)butyl, 5-(2-nitrophenyl)pentyl, 6-(3- nitrophenyl)hexyl, 2-(3,4-dinitrophenyl)ethyl, 2-(3,4,5- trinitrophenyl)ethyl, 2-aminobenzyl, 2-(3-aminophenyl) ethyl, 2-(4-aminopheny1)ethyl, 1-(2-aminopheny1)ethyl, 3-(3-aminophenyl)propyl, 4-(4-aminophenyl)butyl, 5-(2- aminopheny1)pentyl, 6-(3-aminophenyl)hexyl, 2-(3,4- diaminophenyl)ethyl, 2-(3,4,5-triaminophenyl)ethyl, 4- ethylsulfinylbenzyl, 2-(4-methylsulfinyl)ethyl, l-(2- propylsulfinylphenyl)ethyl, 3-(2-butylsulfinylphenyl)- propyl, 4-(3-pentylsulfinylphenyl)butyl, l,l-dimethyl-2- (4-hexylsulfinylphenyl)pentyl, 6-(3-methylsulfinyl¬ phenyl)hexyl, 3-methoxycarbonylbenzyl, 2-(4-methoxy- carbonylphenyl)ethyl, 1-(2-ethoxycarbonylpheny1)ethyl, 3-(3-propoxycarbonylphenyl)propyl, 4-(4-butoxycarbonyl- phenyl)butyl , 5-(2-pentyloxycarbonylphenyl)pentyl, 6-(3- hexyloxycarbonylphenyl)hexyl, 3-carbamoylbenzyl, 2-(4- carbamoylphenyl)ethyl, l-(2-carbamoylphenyl)ethyl, 3-(3- carbamoylphenyl)propyl, 4-(4-carbamoylphenyl)butyl, 5- (2-carbamoylphenyl)pentyl, 6-(3-carbamoylphenyl)hexyl, 3-carboxybenzyl, 2-(4-carboxyphenyl)ethyl, l-(2- carboxyphenyl)ethyl, 3-(3-carboxyphenyl)propyl, 4-(4- carboxyphenyl)butyl, 5-(2-carboxyphenyl)pentyl, 6-(3- carboxyphenyl)hexyl, 2-aminomethoxybenzyl, 2-[2-(2- dimethylaminoethoxy)phenyl]ethyl, l-[3-(3-propylamino propoxy)phenyl]ethyl, 3-[4-(5-hexylaminopentyloxy) phenyl]propyl, 4-{2-[2-(N-methyl-N-pentylamino)ethoxy]- phenyl}butyl, 5-[3-(6-aminohexyloxy)phenyl]pentyl, 3-(2- carboxyethoxy)benzyl, 2-(2-carboxymethoxyphenyl)ethyl, l-[3-(1-carboxyethoxy)phenyl]ethyl, 3-[4-(3-carboxy- propoxy)phenyl]propyl, 4-[2-(4-carboxybutoxy) phenyl]butyl, 5-[3-(5-carboxypentyloxy)phenyl]pentyl, 6- [4-(6-carboxyhexyloxy)phenyl]hexyl, 2-(2-acetyl- aminophenyl)ethyl , 2-(4-acetylaminophenyl)ethyl, 2-(2- methylaminocarbonylaminophenyl)ethyl, 2-(3-acetylamino- phenyl)ethyl, 2-(3-methylaminocarbonylaminophenyl)ethyl, 2-(4-methylaminocarbonylaminophenyl)ethyl, 2-(3-ethoxy- carbonylaminophenyl)ethyl, 1-(2-propionylaminophenyl) ethyl, 3-(3-butyrylaminophenyl)propyl, 4-(4-pentanoyl- aminopheny1)butyl, 5-(5-hexanoylaminophenyl)pentyl, 6- (2-acetylaminophenyl)hexyl, 2-methoxycarbonylamino) benzyl, l-(4-propoxycarbonylaminophenyl)ethyl, 3-(3- butoxycarbonylaminophenyl)propyl, 4-(2-pentyloxy- carbonylaminophenyl)butyl, 5-(3-hexyloxycarbon- ylaminophenyl)benzyl , 6-(2-methoxycarbonylaminophenyl) hexyl, 2-aminocarbonylaminobenzyl, l-(3-propylamino- carbonylaminophenyl)ethyl, 3-(4-hexylaminocarbonyl- aminophenyl)propyl, 4-[2-(N-methyl-N-pentylamino- carbonylamino)phenyl]butyl, 5-(3-dimethylamino- carbonylaminophenyl)pentyl, 6-(2-ethylamino- carbonylaminophenyl)hexyl, 3,4-diacetylaminobenzyl, 3,4- dimethoxycarbonylaminobenzyl, 3-carboxy-4-hydroxybenzyl and 3-methyl-4-methoxybenzyl groups and the like. "Aminocarbonyl group which may have 1-2 substituents selected from the group consisting of lower alkyl groups and phenyl groups" can be exemplified by aminocarbonyl groups which may each have 1-2 substi- tuents selected from the group consisting of C^g straight- or branched-chain alkyl groups and phenyl groups, such as aminocarbonyl, phenylaminocarbonyl, diphenylaminocarbonyl, methylaminocarbonyl, ethylamino¬ carbonyl, propylaminocarbonyl, isopropylaminocarbonyl, butylaminocarbonyl, tert-butylaminocarbonyl , pentyl- aminocarbonyl , hexylaminocarbonyl, dimethylamino- carbonyl, diethylaminocarbonyl, dipropylaminocarbonyl, dibutylaminocarbonyl, dipentylaminocarbonyl, dihexyl- aminocarbonyl, N-methyl-N-ethylaminocarbonyl, N-ethyl-N- propylaminocarbonyl, N-methyl-N-butylaminocarbonyl, N- methyl-N-hexylaminocarbonyl, N-methyl-N-phenylamino- carbonyl and N-ethyl-N-phenylaminocarbonyl groups and the like. "Furoyl group which may have, on the furan ring, substituent(s) selected from the group consisting of a nitro group, a hydroxyl-substituted lower alkyl group, a lower alkanoyl group and an amino groups which may have lower alkanoyl group(s)" can be exemplified by furoyl groups which may each have, on the furan ring, 1- 3 substituents selected form the group consisting of a nitro group, a C x _ 6 straight- or branched-chain alkyl group having 1-3 hydroxyl groups as substituent(s) , C x _ 6 straight- or branched-chain alkanoyl group and an amino group which may have C x _ 6 straight- or branched-chain alkanoyl group(s), such as furoyl, 2-nitrofuroyl, 3- nitrofuroyl, 2,4-dinitrofuroyl, 2-formylfuroyl, 2- acetylfuroyl, 3-propionylfuroyl, 2-butyrylfuroyl, 3- pentanoylfuroyl, 2-hexanoylfuroyl, 2-aminofuroyl, 2,3- diaminofuroyl, 2-propionylaminofuroyl, 3-acetylamino- furoyl, 2-(1-hydroxyethyl)furoyl, 3-hydroxymethylfuroyl, 2-(3-hydroxypropyl)furoyl, 2-butyrylaminofuroyl, 3- pentanoylaminofuroyl, 2-(4-hydroxybutyl)furoyl, 3-(5- hydroxypentyl)furoyl, 2-hexanoylaminofuroyl, 3-nitro-2- acetylaminofuroyl, 3-(5,5,4-trihydroxypentyl)furoyl, 2- (6-hydroxyhexyl)furoyl, 2-(2,3-dihydroxypropyl)furoyl and 2-propionylamino-3,4-dinitrofuroyl groups and the like. "Thienylcarbonyl group which may have, on the thiophene ring, substituent(s) selected from the group consisting of a nitro group, a lower alkyl group, a halogen atom and an amino group which may have lower alkanoyl group(s)" can be exemplified by thienylcarbonyl groups which may each have, on the thienyl ring, 1-3 substituents selected from the group consisting of a nitro group, a C x _ 6 straight- or branched-chain alkyl group, a halogen atom and an amino group which may have C x _ 6 straight- or branched-chain alkanoyl group(s), such as thienylcarbonyl, 2-nitrothienylcarbonyl, 3- nitrothienylcarbonyl, 2,4-dinitrothienylcarbonyl, 2- methylthienylcarbonyl, 3-ethylthienylcarbonyl, 2- propylthienylcarbonyl, 3-butylthienylcarbonyl, 2-pentyl- thienylcarbonyl, 3-hexylthienylcarbonyl, 2,3,4- trimethylthienylcarbonyl, 2,3-dimethylthienylcarbonyl, 2-chlorothienylcarbonyl, 3-bromothienylcarbonyl, 2- fluorothienylcarbonyl, 3-iodothienylcarbonyl, 2,3- dichlorothienylcarbonyl, 2,3,4-trichlorothienylcarbonyl, 2-aminothienylcarbonyl, 2,3-diaminothienylcarbonyl, 2- propionylaminothienylcarbonyl , 3-acetylaminothienyl- carbonyl, 2-butyrylaminothienylcarbonyl, 3-pentanoyl- aminothienylcarbonyl, 2-hexanoylaminothienylcarbonyl, 2- propionylamino-3-methylthienylcarbonyl and 4-chloro-2- acetylaminothienylcarbonyl groups and the like. "Fluorenylcarbonyl group which may have, on the fluorene ring, substituent(s) selected from the group consisting of an oxo group and a nitro group" can be exemplified by fluorenylcarbonyl groups which may each have, on the fluorene ring, 1-3 substituents selected from the group consisting of an oxo group and an nitro group, such as fluorenylcarbonyl, 9- oxofluorenylcarbonyl, 2-nitrofluorenylcarbonyl, 3- nitrofluorenylcarbonyl, 4-nitrofluorenylcarbonyl, 2- nitro-9-oxofluorenylcarbonyl, 3-nitro-9-oxo- fluorenylcarbonyl, 4-nitro-9-oxofluorenylcarbonyl and 2,8-dinitro-9-oxofluorenylcarbonyl groups and the like. "Thienyl-lower alkyl group" can be exemplified by thienylalkyl groups whose alkyl moieties are each a C j .g straight- or branched-chain alkyl group, such as (2-thienyl)methyl, 2-(2-thienyl)ethyl, l-(3-thienyl) ethyl, 3-(2-thienyl)propyl, 4-(3-thienyl)butyl, 5-(2- thienyl)pentyl, 6-(2-thienyl)hexyl, l,l-dimethyl-2-(2- thienyl)ethyl and 2-methyl-3-(3-thienyl)propyl groups and the like. "Furyl-lower alkyl group" can be exemplified by furylalkyl groups whose alkyl moieties are each a C x _ 6 straight- or branched-chain alkyl group, such as (2- furyl)methyl, 2-(2-furyl)ethyl, l-(3-furyl)ethyl, 3-(2- furyl)propyl, 4-(3-furyl)butyl, 5-(2-furyl)pentyl, 6-(2- furyl)hexyl, 1,l-dimethyl-2-(2-furyl)ethyl and 2-methyl- 3-(3-furyl)propyl groups and the like. "Lower alkylene group" can be exemplified by C x _ 6 straight- or branched-chain alkylene groups such as methylene, ethylene, trimethylene, tetra ethylene, pentamethylene, hexamethylene, 2-ethyltrimethylene, 2,2- dimethyltrimethylene, 1-methyltrimethylene, methyl- methylene and ethylmethylene groups and the like. "Phthalimido-substituted lower alkyl group" can be exemplified by phthalimidoalkyl groups whose alkyl moieties are each a C x _ 6 straight- or branched- chain alkyl group, such as phthalimidomethyl, 2- phthalimidoethyl, 1-phthalimidoethyl, 3-phthalimido- propyl, 4-phthalimidobutyl, 5-phthalimidopentyl, 6- phthalimidohexyl, 1,1-dimethyl-2-phthalimidoethyl and 2- methyl-3-phthalimidopropyl groups and the like. "Cycloalkyl-lower alkyl group" can be exempli¬ fied by C 3 -C 8 cycloalkyl-alkyl groups whose alkyl moieties are each a Cj_ 6 straight- or branched-chain alkyl group, such as cyclohexylmethyl, 2-cyclopropyl- ethyl, 2-cyclohexylethyl, 1-cyclobutylethyl, 3- cyclopentylpropyl, 4-cyclohexylbutyl, 2,2-dimethyl-3- cycloheptylpropyl, 5-cyclooctylpentyl and 6-cyclo- hexylhexyl groups and the like. "Phenyl-lower alkenyl group" can be exempli¬ fied by phenylalkenyl groups whose alkenyl moieties are each a C 2 _ 6 straight- or branched-cahin alkenyl group, such as styryl, 3-phenyl-l-propenyl, 3-phenyl-2-pro- penyl, 4-phenyl-3-butenyl, 4-phenyl-2-butenyl, 5-phenyl- 4-pentenyl, 5-phenyl-3-pentenyl, 5-phenyl-2-pentenyl, 6- pheny1-5-hexenyl, 6-phenyl-4-hexenyl, 6-phenyl-3- hexenyl, 6-phenyl-2-hexenyl, 2-methyl-4-phenyl-3- butenyl, 2-methyl-styryl and 1-methyl-styryl groups and the like. "2,3-Dihydro-lH-indenyl group which may have, on the 2,3-dihydro-lH-indene ring, substituent(s) selected from the group consisting of a lower alkoxy group, a hydroxyl group, a nitro group and an amino group which may have lower alkanoyl group(s)" can be exemplified by 2,3-dihydro-lH-indenyl groups which may each have, on the 2,3-dihydro-lH-indene ring, 1-3 substituents selected from the group consisting of a C x _ 6 straight- or branched-chain alkoxy group, a hydroxyl group, a nitro group and an amino group which may have C x _ 6 straight- or branched-chain alkanoyl group(s), such as 2,3-dihydro-lH-indenyl, l-methoxy-2,3-dihydro-lH- indenyl, 5-methoxy-2,3-dihydro-lH-indenyl, 2-ethoxy-2,3- dihydro-lH-indenyl, 3-methoxy-2,3-dihydro-lH-indenyl, 6- ethoxy-2,3-dihydro-lH-indenyl, 4-propoxy-2,3-dihydro-lH- indenyl, 7-butoxy-2,3-dihydro-lH-indenyl, 5-pentyloxy- 2,3-dihydro-lH-indenyl , 6-hexyloxy-2,3-dihydro-lH- indenyl, 3,5,7-trimethoxy-2,3-dihydro-lH-indenyl, 5,7- dimethoxy-2,3-dihydro-lH-indenyl, 5-hydroxy-2,3-dihydro- lH-indenyl, 6-hydroxy-2,3-dihydro-lH-indenyl, 4-hydroxy- 2,3-dihydro-lH-indenyl, 7-hydroxy-2,3-dihydro-lH- indenyl, l-hydroxy-2,3-dihydro-lH-indenyl, 2-hydroxy- 2,3-dihydro-lH-indenyl, 3-hydroxy-2,3-dihydro-lH- indenyl, l,3,5-trihydroxy-2,3-dihydro-lH-indenyl, 3,5- dihydroxy-2,3-dihydro-lH-indenyl, 1-nitro-2,3-dihydro- lH-indenyl, 2-nitro-2,3-dihydro-lH-indenyl, 3-nitro-2,3- dihydro-lH-indenyl, 4-nitro-2,3-dihydro-lH-indenyl, 5- nitro-2,3-dihydro-lH-indenyl, 6-nitro-2,3-dihydro-lH- indenyl, 7-nitro-2,3-dihydro-lH-indenyl, 5,7-dinitro- 2,3-dihydro-lH-indenyl, l-amino-2,3-dihydro-lH-indenyl, 2-amino-2 ,3-dihydro-lH-indenyl, 3-amino-2,3-dihydro-lH- indenyl, 4-amino-2,3-dihydro-lH-indenyl, 5-amino-2,3- dihydro-lH-indenyl, 6-amino-2,3-dihydro-lH-indenyl, 7- amino-2,3-dihydro-lH-indenyl, 1,5-diamino-2,3-dihydro- lH-indenyl, l,2,5-triamino-2,3-dihydro-lH-indenyl, 5- acetylamino-2,3-dihdyro-lH-indenyl, 2-propionylamino- 2,3-dihydro-lH-indenyl, l-butyrylamino-2,3-dihydro-lH- indenyl, 3-pentanoylamino-2,3-dihydro-lH-indenyl, 4- hexanoylamino-2 ,3-dihydro-lH-indenyl, 6-acetylamino-2,3- dihydro-lH-indenyl, 7-formylamino-2,3-dihydro-lH- indenyl, 2,5-diacetylamino-2,3-dihydro-lH-indenyl, 1- hydroxy-5-amino-2,3-dihydro-lH-indenyl, l-methoxy-5- nitro-2,3-dihydro-lH-indenyl and l-hydroxy-5-acetyl- amino-2,3-dihydro-lH-indenyl groups and the like. "Phenyl-lower alkoxy group" can be exemplified by phenylalkoxy groups whose alkoxy moieties are each a C x _ 6 straight- or branched-chain alkoxy group, such as benzyloxy, 2-phenylethoxy, 1-phenylethoxy, 3-phenyl- propoxy, 4-phenylbutoxy, l,l-dimethyl-2-phenylethoxy, 5- phenylpentyloxy, 6-phenylhexyloxy and 2-methyl-3-phenyl- propoxy groups and the like. "Lower alkanoyloxy group" can be exemplified by C x _ 6 striaght- or branched-chain alkanoyloxy groups such as formyloxy, acetyloxy, propionyloxy, butyryloxy, isobutyryloxy, pentanoyloxy, tert-butylcarbonyloxy and hexanoyloxy groups and the like. "Phenyl-lower alkoxycarbonyl group" can be exemplified by phenylalkoxycarbonyl groups whose alkoxycarbonyl moieties are each a C x _ 6 straight- or branched-chain akoxycarbonyl group, such as benzyloxy- carbonyl, 2-phenylethoxycarbonyl, 1-phenylethoxy- carbonyl, 3-phenylpropoxycarbonyl, 4-phenylbutoxy- carbonyl, 1,1-dimethyl-2-phenylethoxycarbonyl, 5- phenylpentyloxycarbonyl, 6-phenylhexyloxycarbonyl and 2- methyl-3-phenylpropoxycarbonyl groups and the like. "Amino-lower alkyl group which may have substituent(s) selected from the group consisting of a lower alkyl group and a lower alkanoyl group" can be exemplified by C x _ 6 straight- or branched-chain alkyl groups each having an amino group which may have 1-2 substituents selected from the group consisting of a C x _ 6 straight- or branched-chain alkyl group and a C x _ 6 straight- or branched-chain alkanoyl group, such as aminomethyl, 2-aminoethyl, 1-aminoethyl, 3-aminopropyl, 4-aminopropyl, 5-aminopentyl, 5-aminohexyl, 1,1- dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, methyl- aminomethyl, ethylaminomethyl, 1-ethylaminoethyl, 2- propylaminoethyl, 3-isopropylaminopropyl, 4-butylamino- butyl, 5-pentylaminopentyl, 6-hexylaminohexyl, dimethyl- aminomethyl, 2-diethylaminoethyl, 2-dimethylaminoethyl, (N-ethyl-N-propylamino)methyl, 2-(N-methyl-N-hexylamino) ethyl, formylaminomethyl, acetylaminomethyl, 1-acetyl- aminoethyl, 2-propionylaminoethyl, 3-butyrylaminopropyl, 4-pentanoylaminobuty1, 5-hexanoylaminopentyl , 6-acetyl- aminohexyl and (N-ethyl-N-acetylamino)methyl groups and the like. "Cycloalkyl group which may have phenyl group(s)" can be exemplified by C 3 . 8 cycloalkyl groups which may each have phenyl group(s), such as cyclo- propyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclo- heptyl, cyclooctyl, 1-phenylcyclopropyl, 1-phenylcyclo¬ butyl, 1-phenylcyclopentyl, 1-phenylcyclohexyl, 1- phenyleyeloheptyl and 1-phenylcyclooctyl groups and the like . "Furoyl group having, on the furan ring, substituent(s) selected from the group consisting of a nitro group, a hydroxyl-substituted lower alkyl group, a lower alkanoyl group and a amino group which may have lower alkanoyl group(s)" can be exemplified by the above-mentioned furoyl groups other than unsubstituted furoyl group. "Phenyl-C 1 _ 2 alkyl group" can be exemplified by benzyl, 1-phenylethyl and 2-phenylethyl groups and the like. "Phenyl-lower alkyl group having lower alkylthio group(s) on the phenyl ring" can be exem¬ plified by phenylalkyl groups which each have, on the phenyl ring, one to three C x _ 6 straight- or branched- chain alkylthio groups and whose alkyl moieties are each a Cj.g straight- or branched-chain alkyl group, such as 4-ethylthiobenzyl, 2-(4-methylthiophenyl)ethyl, l-(2- propy1thiophenyl)ethyl, 3-(2-butylthiophenyl)propyl, 4- (3-pentylthiophenyl)butyl, 1,1-dimethyl-2-(4-hexylthio- phenyl)ethyl, 5-(2-methylthiophenyl)pentyl, 6-(3-methyl- thiophenyl)hexyl , 3,4-dimethylthiobenzyl and 2,4,6- trimethylthiobenzyl groups and the like. "Cycloalkyl group having phenyl group(s)" can be exemplified by the above-mentioned cycloalkyl groups which may each have phenyl ring(s), other than unsub¬ stituted cycloalkyl groups. The compounds of the present invention represented by general formula (1) can be produced by various processes. Preferable processes for production of said compounds include, for example, the followings. [Reaction formula-1] [wherein, Ra represents a group of the formula: (wherein, R 3 and m are the same as defined above); a lower alkanoyl group which may have hydroxyl group(s) or amino group(s) which may each have lower alkyl group(s) as substituent(s) ; a lower alkanoyl group having 1-3 halogen atoms; a lower alkoxycarbonyl group; a pyridyl¬ carbonyl group which may have, on the pyridine ring, substituent(s) selected from the group consisting of a nitro group, an amino group which may have lower alkanoyl group(s) as substituent(s) , a halogen atom, a lower alkyl group, a pyrrolyl group, a lower alkylthio group, a lower alkanoyl group, a hydroxyl group, a aminocarbonyl group which may have lower alkyl group(s) as substituent(s) , a lower alkoxycarbonyl group, a hydroxyl-substituted lower alkyl group, a phenyl group and a 1,2,4-triazolyl group; a 1,2,4-triazolyl-lower alkanoyl group; a furoyl group which may have, on the furan ring, substituent(s) selected from the group 5 consisting of a nitro group, a hydroxyl-substituted lower alkyl group, a lower alkanoyl group and an amino group which may have lower alkanoyl group(s) as substituent(s) ; a thienylcarbonyl group which may have, on the thiophene ring, substituent(s) selected from the 0 group consisting of a nitro group, a lower alkyl group, a halogen atom and an amino group which may have lower ( alkanoyl group(s) as substituent(s); a fluorenylcarbonyl group which may have, on the fluorene ring, substi- tuent(s) selected from the group consisting of an oxo group and a nitro group; or a group of the formula (wherein, Y, , Z, the dotted line in the bond - , and /Y the substituent(s) on the group of the formula: are the same as mentioned above); and R 1 and R 2 are the same as defined above] The process shown by the above reaction formula 1 is carried out by reacting a carboxylic acid derivative represented by general formula (2) or a compound obtained by activating the carboxyl group of said derivative, with an amine represented by general formula (3) or a compound obtained by activating the amino group of said amine, according to an ordinary amido-bond formation reaction. In the reaction, the known conditions used in amido-bond formation reaction can be employed easily. The process includes, for example, (a) a mixed acid anhydride process which com¬ prises reacting a carbostyril derivative (2) with an alkylhaloearboxylic acid to form a mixed acid anhydride and reacting the anhydride with an amine (3); (b) an active ester process which comprises converting a carbostyril derivative (2) into an active ester such as p-nitrophenyl ester, N-hydroxysuccinimide ester, 1- hydroxybenzotriazole ester or the like and reacting the active ester with an amine (3); (c) a carbodiimide process which comprises subjecting a carbostyril derivative (2) and an amine (3) to a condensation reaction in the presence of an activating agent such as dicyclohexylcarbodiimide, carbonyldiimidazole or the like; and (d)- other processes. The other processes (d) include, for example, a process which comprises convert- ing a carbostyril derivative (2) into a carboxylic acid anhydride using a dehydrating agent such as acetic anhydride or the like and reacting the carboxylic acid anhydride with an amine (3); a process which comprises reacting an ester of a carboxylic acid derivative (2) and a lower alcohol with an amine (3) at a high pressure at a high temperature; and a process which comprises reacting an acid halide of a carboxylic acid derivative (2), i.e. a carboxylic acid halide with an amine (3) . There may be also employed, for example, a process which comprises activating a carboxylic acid derivative (2) with a phosphorus compound such as triphenylphosphine, diethyl cyanophosphonate, diethyl chlorophosphate, N,N- bis(2-oxo-3-oxazolidinyl)phosphorodiamidic chloride, diphenylphosphoramide or the like and reacting the resulting compound with an amine (3) . The mixed acid anhydride used in the mixed acid anhydride process (a) can be obtained by an ordinary Schotten-Baumann reaction. The anhydride is reacted with an amine (3) generally without being isolated, whereby a compound of general formula (1) can be produced. The Schotten-Baumann reaction is conducted in the presence or absence of a basic compound. The basic compound is a compound conventionally used in the Schotten-Baumann reaction and includes, for example, organic bases such as triethylamine, trimethylamine, pyridine, dimethylaniline, N-methylmorpholine, 4- dimethylaminopyridine, 1,5-diazabicyclo[4.3.0]nonene-5 (DBN), l,8-diazabicyclo[5.4.0]undecene-7 (DBU), 1,4- diaza-bicyclo[2.2.2]octane (DABCO) and the like, and inorganic bases such as potassium carbonate, sodium carbonate, potassium hydrogencarbonate, sodium hydrogencarbonate and the like. The reaction is conducted generally at -20°C to 100°C, preferably at 0- 50°C, and the reaction time is 5 minutes to 10 hours, preferably 5 minutes to 2 hours. The reaction of the resulting mixed acid anhydride with an amine (3) is conducted generally at -20°C to 150°C, preferably at 10- 50°C, and the reaction time is 5 minutes to 10 hours, preferably 5 minutes to 5 hours. Th.e mixed acid anhydride process (a) is conducted in an appropriate solvent or in the absence of any solvent. The solvent may be any solvent conventionally used in the mixed acid anhydride process, and can be exemplified by halogenated hydrocarbons such as methylene chloride, chloroform, dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dimethoxyethane and the like; esters such as methyl acetate, ethyl acetate and the like; and aprotic polar solvents such as N,N- dimethylformamide, dimethyl sulfoxide, hexamethylphos- phoric triamide and the like. The alkylhaloearboxylic acid used in the mixed acid anhydride process (a) includes, for example, methyl chloroformate, methyl bromoformate, ethyl chloroformate, ethyl bromoformate and isobutyl chloroformate. The alkylhaloearboxylic acid is used in an amount of generally at least 1 mole, preferably about 1-2 moles per mole of the carbostyril derivative (2) . The amine (3) is used in an amount of generally at least 1 mole, preferably about 1-2 moles per mole of the carboxylic acid derivative (2) . The active ester process (b), when, for exam¬ ple, N-hydroxysuccinimide ester is used, is conducted in an appropriate solvent which does not adversely affect the reaction. Specific examples of the solvent are halogenated hydrocarbons such as methylene chloride, chloroform, dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dimethoxyethane and the like; esters such as methyl acetate, ethyl acetate and the like; and aprotic polar solvents such as N,N-dimethylformamide, dimethyl sulfoxide, hexamethylphosphoric triamide and the like. The reaction is conducted at 0-150°C, preferably at 10- 100°C and is complete in 5-30 hours. With respect to the desirable proportions of the amine (3) and the N- hydroxysuccinimide ester, the former is used in an amount of generally at least 1 mole, preferably 1-2 moles per mole of the latter. The process which comprises reacting a carboxylic acid halide with an amine (3) [this is a process included in the other processes (d)], can be conducted in the presence of a dehydrohalogenating agent in an appropriate solvent. As the dehydrohalogenating agent, an ordinary basic compound is used. The basic compound can be selected from various known basic compounds and can be exemplified by not only the basic compounds usable in the above Schotten-Baumann reaction but also sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, silver carbonate and alcoholates (e.g. sodium methylate and sodium ethylate). The solvent can be exemplified by the solvents usable in the mixed acid anhydride process (a), alcohols (e.g. methanol, ethanol, propanol, butanol, 3-methoxy-l- butanol, ethyl cellosolve and methyl cellosolve), water, pyridine, acetone, acetonitrile and mixtures thereof. The proportions of the amine (3) and the carboxylic acid halide used are not particularly restricted and can be appropriately selected from a wide range, but the carboxylic acid halide is used in an amount of generally at least about 1 mole, preferably about 1-2 moles per mole of the amine (3) . The reaction is conducted generally at about -30°C to 180°C, preferably at about 0- 150°C and is complete generally in about 5 minutes to 30 hours. In the above process, the carboxylic acid halide can be produced, for example, by reacting a carboxylic acid derivative (2) with a halogenating agent in the presence or absence of a solvent. The solvent may be any solvent which does not adversely affect the reaction, and includes, for example, aromatic hydro¬ carbons (e.g. benzene, toluene and xylene), halogenated hydrocarbons (e.g. chloroform, methylene chloride and carbon tetrachloride) , ethers (e.g. dioxane, tetrahydro- furan and diethyl ether), aprotic polar solvents (e.g. N,N-dimethylformamide and dimethyl sulfoxide) and mixtures thereof. The halogenating agent may be an ordinary halogenating agent used for converting the hydroxyl group of carboxyl group into a halogen atom, and can be exemplified by thionyl chloride, phosphorus oxychloride, phosphorus oxybromide, phosphorus penta- chloride and phosphorus pentabromide. The proportions of the carboxylic acid derivative (2) and the halogenat¬ ing agent used are not particularly restricted and can be appropriately selected. The latter is used generally in large excess of the former when the reaction is conducted in the absence of any solvent, and in an amount of generally at least about 1 mole, preferably 2- 4 moles per mole of the former when the reaction is conducted in a solvent. The reaction temperature and reaction time are not particularly restricted, either. However, the reaction temperature is generally about room temperature to 150°C, preferably room temperature to 100°C and the reaction time is about 10 minutes to 6 hours. The process which comprises activating a carboxylic acid derivative (2) with a phosphorus compound such as triphenylphosphine, diethyl cyano- phosphate, diethyl chlorophosphonate, N,N-bis(2-oxo-3- oxazolidinyl)phosphinic acid chloride, diphenyl phosphoryl azide or the like and reacting the resulting compound with an amine (3) , can be conducted in an appropriate solvent. The solvent can be any solvent which does not adversely affect the reaction. Specific examples thereof are halogenated hydrocarbons such as methylene chloride, chloroform, dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dimethoxyethane and the like; esters such as methyl acetate, ethyl acetate and the like; and aprotic polar solvents such as N,N-dimethylformamide, dimethyl sulfoxide, hexamethylphosphoric triamide and the like. In the reaction, since the amine (3) acts also as a basic compound, the use of the amine (3) in excess of the stoichiometric amount allows the reaction to proceed favorably. However, it is possible to use, as necessary, other basic compound, for example, an organic base (e.g. triethylamine, trimethylamine, pyridine, dimethylaniline, N-methyImorpholine, DBN, DBU or DABCO) or an inorganic base (e.g. potassium carbon¬ ate, sodium carbonate, potassium hydrogencarbonate or sodium hydrogencarbonate). The reaction is conducted at about 0-150°C, preferably at about 0-100°C and is com- plete in about 10 minutes to 30 hours. The phosphorus compound and the amine (3) are used each in an amount of generally at least about 1 mole, preferably 1-3 moles per mole of the carboxylic acid derivative (2) . [Reaction formula-2 ] (4) (3) (1b) (wherein, R 1 , R 2 , R 6 and X are the same as defined above) . The reaction of the compound (3) with the compound (4) is conducted in the presence or absence of a basic compound, preferably in the absence of any basic compound, in an appropriate solvent or in the absence of any solvent. The solvent and basic compound can each be any of those mentioned with respect to the Reaction formula-1 process for reacting a carboxylic acid halide with an amine (3) . The desirable amount of the compound (4) is generally about 1-15 moles, preferably about 1-10 moles per mole of the compound (3). The reaction is conducted generally at about 0-200°C, preferably at about room temperature to 150°C generally in about 5 minutes to 30 hours. In the reaction, a boron compound such as boron trifluoride-diethyl ether or the like may be added. [Reaction formula-3] (5) (6) (1) (wherein, R, R 1 and R 2 are the same as defined above), (a) The reaction of the compound of general formula (5) with the compound of general formula (6) is conducted in the absence of any solvent or in the presence of an appropriate solvent, in the presence or absence of a dehydrating agent. The solvent includes, for example, alcohols such as methanol, ethanol, isopropanol and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, carbon tetrachloride and the like; aprotic polar solvents such as N,N-dimethylformamide, N,N- dimethylacetamide, N-methylpyrrolidone and the like; and mixed solvents thereof. The dehydrating agent includes, for example, drying agents conventionally used for dry¬ ing of solvents, such as molecular sieve and the like; mineral acids such as hydrochloric acid, sulfuric acid and the like; Lewis acids such as boron trifluoride and the like; and organic acids such as p-toluenesulfonic acid and the like. The reaction is conducted generally at room temperature to 250°C, preferably at about 50- 200°C and is complete generally in about 1-48 hours. The amount of the compound of general formula (6) used is not particularly restricted but desirably is generally at least equimolar, preferably equi olar to a large excess over the compound of general formula (5). The desirable amount of the dehydrating agent used is generally a large excess when a drying agent is used, and is a catalytic amount when an acid is used. The above reaction produces a Schiff base as an intermediate. The intermediate is reduced to convert to a desired compound (1). Various methods can be employed for this reduction and, for example, a method using a hydride as a reducing agent is preferably used. The hydride includes, for example, lithium aluminum hydride, sodium boron hydride and diborane. The amount of the hydride used is generally at least 1 mole, preferably 1-15 moles per mole of the compound (5). The reduction is conducted generally using an appropriate solvent such as water, lower alcohol (e.g. methanol, ethanol or isopropanol), ether (e.g. tetrahydrofuran, diethyl ether or diglyme) or the like generally at about -60°C to 50°C, preferably at -30°C to room temperature for about 10 minutes to 15 hours. When lithium aluminum hydride or diborane is used as a reducing agent, it is preferable to use an anhydrous solvent such as diethyl ether, tetrahydrofuran, diglyme or the like. (b) When the above reaction of the compound. (5) with the compound (6) is conducted in the absence of any solvent or in the presence of an appropriate solvent in the presence of a reducing agent, a compound (1) can be obtained in one step. The solvent can be exemplified by water; alcohols such as methanol, ethanol, iso¬ propanol and the like; acetic acid; ethers such as dioxane, tetrahydrofuran, diethyl ether, diglyme and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; and mixed solvents thereof. The reaction can be conducted by, for example, a process using formic acid or a hydride reducing agent such as sodioum borohydride, sodium cyanoborohydride, lithium aluminum hydride or the like, and a catalytic reduction process using a catalytic reduction catalyst such as palladium black, palladium carbon, platinum oxide, platinum black, platinum carbon, Raney nickel or the like. When formic acid is used as the reducing agent, the reaction is conducted generally at about room temperature to 200°C, preferably at about 50-150°C and is complete in about 1-10 hours. The desirable amount of formic acid used is a large excess over the compound of general formula (5). When a hydride reducing agent is used, the reaction is conducted generally at about -30°C to 100°C, preferably at about 0-70°C and is complete in about 30 minutes to 12 hours. The desirable amount of the reducing agent used is generally 1-20 moles, preferably 1-5 moles per mole of the compound of general formula (5). When lithium aluminum hydride is used as the reducing agent, it is preferable to use, as the solvent, for example, an ether (e.g. dioxane, tetrahydrofuran, diethyl ether or diglyme) or an aromat¬ ic hydrocarbon (e.g. benzene, toluene or xylene). When a catalytic reduction catalyst is used, the reaction is conducted in a hydrogen atmosphere of generally normal pressure to 20 atm., preferably normal pressure to 10 atm. generally at -30°C to 100°C, preferably at 0-60°C. The desirable amount of the catalyst used is generally 0.1-40% by weight, preferably 0.1-20% by weight based on the compound of general formula (5) . The amount of the compound (5) used is not particularly restricted and can be appropriately selected from a wide range, but desirably is generally at least equimolar to the compound of general formula (6), preferably equimolar to a large excess over the compound (6) . [ Reaction formula-4 ] R >1 ι a a Xτ (7) (1c) (1 d) [wherein, R is the same as defined above; R 2a represents a hydrogen atom; a lower alkyl group which may have hydroxyl group(s) as substituent(s); a phenyl-lower alkyl group which may have, on the phenyl ring, substituent(s) selected from the group consisting of a lower alkoxy group, a halogen atom, a hydroxyl group, a nitro group, a lower alkyl group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkoxycarbonyl group, a carbamoyl group, a carboxy group, an amino-lower alkoxy group which may have lower alkyl group(s) as substituent(s) , a carboxy-substituted lower alkoxy group and an amino group which may have, as substituent(s) , lower alkanoyl group(s), lower alkoxy- carbonyl group(s), or aminocarbonyl group(s) which may each have lower alkyl group(s) as substituent(s) , which phenyl-lower alkyl group may have lower alkoxycarbonyl group(s) or hydroxyl-substituted lower alkyl group(s) as substituent(s) in the lower alkyl moiety; a phenoxy- lower alkyl group which may have, on the phenyl ring, substituent(s) selected from the group consisting of a lower alkoxy group, a lower alkyl group, a halogen atom. a nitro group, a hydroxyl group and an amino group which may have lower alkanoyl group(s) as substituent(s) ; a pyridyl-lower alkyl group which may have lower alkyl group(s) as substituent(s) on the pyridine ring; a thienyl-lower alkyl group; a furyl-lower alkyl group; a group of the formula: R 27 / -B-N 28 (wherein, B, R 27 and R 28 are the same as defined above); a phthalimido-substituted lower alkyl group; a cycloalkyl-lower alkyl group; a phenyl-lower alkenyl group; a cycloalkyl group which may have a phenyl group as a substituent; or a 2,3-dihydro-lH-indenyl group which may have, on the 2,3-dihydro-lH-indene ring, substituent(s) selected from the group consisting of a lower alkoxy group, a hydroxyl group, a nitro group and an amino group which may have lower alkanoyl group(s); R la represents the above-mentioned R 2 other than hydrogen atom; and X 1 represents a halogen atom, a lower- alkanesulfonyloxy group, an arylsulfonyloxy group or an aralkylsulfonyloxy group, provided that, when R 2a is the same as defined above, except a hydrogen atom and a lower alkyl group which may have hydroxyl group(s) as substituent(s) , then R la should be a lower alkyl group which may have hydroxyl group(s) as substituent(s) ; further, when R a is a hydrogen atom or a lower alkyl group which may have hydroxyl group(s) as substi- tuent(s), then R la should be the same as defined above, except a lower alkyl group which may have hydroxyl group(s) as substituent(s) ] . In the compound represented by the above general formula (7), specific examples of the halogen atom represented by X 1 are chlorine, fluorine, bromine and iodine atoms; specific examples of the lower alkane- sulfonyloxy group are methanesulfonyloxy, ethane- sulfonyloxy, propanesulfonyloxy, isopropanesulfonyloxy, butanesulfonyloxy, tert-butanesulfonyloxy, pentane- sulfonyloxy and hexanesulfonyloxy; specific examples of the arylsulfonyloxy group are substituted or unsubsti- tuted arylsulfonyloxy groups such as phenylsulfonyloxy, 4-methylphenylsulfonyloxy, 2-methylphenylsulfonyloxy, 4- nitrophenylsulfonyloxy, 4-methoxyphenylsulfonyloxy, 3- chlorophenylsulfonyloxy, α-naphthylsulfonyloxy and the like; and specific examples of the aralkylsulfonyloxy group are substituted or unsubstituted aralkyl- sulfonyloxy groups such as benzylsulfonyloxy, 2- phenylethylsulfonyloxy, 4-phenylbutylsulfonyloxy, 4- methylbenzylsulfonyloxy, 2-methylbenzylsulfonyloxy, 4- nitrobenzylsulfonyloxy, 4-methoxybenzylsulfonyloxy, 3- chlorobenzylsulfonyloxy, α-naphthylmethylsulfonyloxy and the like. The reaction of the compound of general formula (lc) with the compound of general formula (7) is conducted generally in an appropriate inert solvent, in the presence or absence of a basic compound. The inert solvent can be exemplified by aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as tetrahydrofuran, dioxane, diethylene glycol dimethyl ether and the like; lower alcohols such as methanol, ethanol, isopropanol, butanol and the like; acetic acid; ethyl acetate; acetone; acetonitrile; dimethyl sulf- oxide; N,N-dimethylformamide; hexamethylphosphoric triamide; and the like. The basic compound can be exemplified by alkali metal carbonates such as sodium carbonate, potassium carbonate, sodium hydrogen¬ carbonate, potassium hydrogencarbonate and the like; alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and the like; sodium hydride; potassium; sodium; sodium amide; metal alcholates such as sodium methylate, sodium ethylate and the like; and organic bases such as pyridine, diisopropylethylamine, dimethylaminopyridine, triethylamine, 1,5-diazabicyclo- [4.3.0]nonene-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), l,4-diazabicyclo[2.2.2]octane (DABCO) and the like. The proportions of the compound of general formula (lc) and the compound of general formula (7) used are not particularly restricted and can be appro¬ priately selected from a wide range, but it is desirable to use the latter compound in an amount of at least about 1 mole, preferably about 1-5 moles per mole of the former. The reaction is conducted generally at about 0- 200°C, preferably at about 0-170°C and is complete generally in about 30 minutes to 30 hours. An alkali metal halide such as sodium iodide, potassium iodide or the like may be added to the reaction system. [Reaction formula-5] (11) [wherein, R and R 2 are the same as defined above; R lb represents a phenyl group which may have, on the phenyl ring, substituent(s) selected from the group consisting of a lower alkoxy group, a halogen atom, a hydroxyl group, a nitro group, a lower alkyl group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkoxycarbonyl group, a carbamoyl group, a carboxy group, an amino-lower alkoxy group which may have lower alkyl group(s) as substituent(s) , a carboxy- substituted lower alkoxy group and an amino group which may have, as substituent(s) , lower alkanoyl group(s), lower alkoxycarbonyl group(s) or aminocarbonyl group(s) which may each have lower alkyl group(s) as subst- ituent(s); a pyridyl group which may have lower alkyl group(s) as substituent(s) on the pyridine ring; a thienyl group; a furyl group; a phthalimido group; a cycloalkyl group; or the above-mentioned R 2 " group other than hydrogen atom, 2,3-dihydro-lH-indenyl group which may have, on the 2,3-dihydro-lH-indene ring, substit¬ uent(s) selected from the group consisting of a lower alkoxy group, a hydroxyl group, a nitro group and an amino group which may have lower alkanoyl group(s) as substituent(s) , a phenyl-lower alkyl group which may have, on the phenyl ring, substituent(s) selected from the group consisting of a lower alkoxy group, a halogen atom, a hydroxyl group, a nitro group, a lower alkyl group a lower alkylthio group, a lower alkylsulfinyl group, a lower alkoxycarbonyl group, a carbamoyl group, a carboxy group, an amino-lower alkoxy group which may have lower alkyl group(s) as substituent(s) , a carboxy group-substituted lower alkoxy group and an amino group which may have substituent(s) selected from the group consisting of a lower alkanoyl group, a lower alkoxy¬ carbonyl group and aminocarbonyl group(s) which may each have lower alkyl group(s) as substituent(s), which phenyl-lower alkyl group has lower alkoxycarbonyl group(s) or hydroxyl group-substituted lower alkyl group(s) as substituent(s) in the lower alkyl moiety, and cycloalkyl group which may have phenyl group(s) as substituent(s) ; R lc represents the above-mentioned R 2a group other than hydrogen atom and 2,3-dihydro-lH-indenyl group which may have, on the 2,3-dihydro-lH-indene ring, substituent(s) selected from the group consisting of a lower alkoxy group, a hydroxyl group, a nitro group, an amino group which may have lower alkanoyl group(s) as substituent(s) ; a phenyl-lower alkyl group which may have, on the phenyl ring, substituent(s) selected from the group consisting of a lower alkoxy group, a halogen atom, a hydroxyl group, a nitro group, a lower alkyl group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkoxycarbonyl group, a carbamoyl group, a carboxy group, an amino-lower alkoxy group which may have lower alkyl group(s) as substituent(s) , a carboxy group-substituted lower alkoxy group and an amino group which may have substituent(s) selected from the group consisting of a lower alkanoyl group, a lower alkoxy¬ carbonyl group and aminocarbonyl group(s) which may each have lower alkyl group(s) as substituent(s) , which phenyl-lower alkyl group has lower alkoxycarbonyl group(s) or hydroxy group-substituted lower alkyl group(s) as substituent(s) in the alkyl moiety; and a cycloalkyl group which may have phenyl group(s) as substituen(s); R 8 and R 9 independently represent a hydrogen atom or a lower alkyl group provided that, in compound (le), R 2a is a hydrogen atom or a lower alkyl group which may have hydroxyl group(s) as substituent(s) , further, in compound (If), R 2a is the same as defined above, except both a hydrogen atom and a lower alkyl group which may have hydroxyl group(s) as substituent(s)] . The reaction of the compound (lc) with the compound (8) can be conducted under the same conditions as used in the reaction of the compound (5) with the compound (6) by the process (a) in the reaction formula- 3. The reaction of the compound (lc) with the compound (9) can be conducted under the same conditions as used in the reaction of the compound (5) with the compound (6) by the process (b) in the Reaction formula-3. [Reaction formula-6 ] (tfϊ p [wherein, R 1 , R 2 , R 3 , R 5 , R 8 , R 9 and X 1 are the same as defined above; p is an integer of 1-2; R* a represents a lower alkanoyl group, a lower alkanoyl group having 1-3 halogen atoms as substituent(s) , a benzoyl group, a pyridylcarbonyl group or a lower alkenylcarbonyl group; R* b represents a lower alkyl group; R 4c represents a phenyl group or a lower alkyl group; and R d represents a lower alkyl group, a phenyl group or a lower alkenyl group] . The reaction of the compound (lg) with the compound (10) can be conducted under the same conditions as used in the reaction of the compound (2) with the compound (3) in the Reaction formula-1. The reaction of the compound (lg) with the compound (11) can be conducted under the same conditions as used in the reaction of the compound (lc) with the compound (7) in the Reaction formula-4. The reaction of the compound (lg) with the compound (9) can be conducted under the same conditions as used in the reaction of the compound (lc) with the compound (9) in the Reaction formula-5. The reaction of the compound (lg) with the compound (12) or the compound (13) can be conducted under the same conditions as used in the reaction of the compound (4) with the compound (3) in the Reaction formula-2. [Reaction formula-7] < 1A > (1 m) (wherein R 1 , R 2 , R 6 , X and X 1 are the same as defined above; and R 7a represents a lower alkyl group). The reaction of the compound ( It ) with the compound (14) can be conducted under the same conditions as used in the reaction of the compound (lc) with the compound (7) in the Reaction formula-4. [Reaction formula-8] (wherein, R 1 , R 2 , R 3 and p are the same as defined above) . The reduction of the compound (If') is con- ducted, for example, (1) using a catalytic reduction catalyst in an appropriate solvent, or (2) using, as a reducing agent, a mixture between a metal or a metal salt and an acid, or between a metal or a metal salt and an alkali metal hydroxide, a sulfide, an ammonium salt or the like in an appropriate inert solvent. (1) When the reduction is conducted by the above method using a catalytic reduction catalyst in an appropriate solvent, the solvent includes, water; acetic acid; alcohols such as methanol, ethanol, isopropanol and the like; hydrocarbons such as hexane, cyclohexane and the like; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride and the like; ethers such as dioxane, tetrahydrofuran, diethyl ether, diethylene glycol dimethyl ether and the like; esters such as ethyl acetate, methyl acetate and the like; aprotic polar solvents such as N,N-dimethylformamide and the like; and mixed solvents thereof. The catalytic reduction catalyst includes, for example, palladium, palladium hydroxide carbon, palladium black, palladium- carbon, platinum, platinum oxide, copper chro ite and Raney nickel. The desirable amount of the catalyst used is generally about 0.02-1 time the amount of the start¬ ing material. The reaction temperature is generally about -20°C to 150°C, preferably about 0-100°C, and the hydrogen pressure is generally 1-10 atm. The reaction is complete generally in about 0.5-24 hours. An acid such as hydrochloric acid or the like may be added in the reaction. (2) When the reduction is conducted by the above method using a reducing agent in an appropriate inert solvent, the reducing agent includes, for example, a mixture between iron, zinc, tin or stannous chloride and an acid (e.g. hydrochloric acid or sulfuric acid), and a mixture between iron, ferrous sulfate, zinc or tin and an alkali metal hydroxide (e.g. sodium hydroxide), a sulfide (e.g. ammonium sulfide), ammonia water or an ammonium salt (e.g. ammonium chloride). The solvent can be exemplified by water, acetic acid, methanol, ethanol and dioxane. The conditions for reduction can be appropriately selected depending upon the type of the reducing agent used. For example, when a mixture of stannous chloride and hydrochloric acid is used as a reducing agent, the reaction can be conducted favorably by employing a reaction temperature of about 0°C to 100°C and a reaction time of about 0.5-10 hours. The reducing agent is used in an amount of at least 1 mole, generally 1-5 moles per mole of the starting material compound. [ Reaction formula-9 ] OH (1n) (1o) (wherein, R 1 , R 2 , R 3 , X 1 and p are the same as defined above; R 12 represents a lower alkoxy group, a phenyl- lower alkoxy group or a lower alkanoyl group; and R 13 represents a lower alkyl group, a phenyl-lower alkyl group, a lower alkanoyl group, an amino-lower alkyl group which may have lower alkyl group(s) as substi¬ tuent(s), or a morpholinyl-substituted lower alkyl group) . The reaction for converting a compound (In) wherein R 12 is a lower alkoxy group, into a compound (lo) , can be conducted by heat-treating the compound (In) at 30-150°C, preferably at 50-120°C in a mixture of an acid (e.g. hydrobromic acid or hydrochloric acid) and a solvent (e.g. water, methanol, ethanol, ispropyl alcohol or acetic acid). Alternatively, the reaction can be conducted by hydrolyzing the compound (In). The hydrolysis is conducted in the presence of an appro¬ priate solvent in the presence of an acid. The solvent includes, for example, water; lower alcohols such as methanol, ethanol, isopropyl alcohol and the like; ethers such as dioxane, tetrahydrofuran and the like; halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride and the like; polar solvents such as acetonitrle and the like; and mixed solvents thereof. The acid includes, for example, mineral acids such as hydrochloric acid, sulfuric acid, hydrobromic acid and the like; Lewis acids such as boron trifluoride, aluminum chloride, boron trifluoride and the like; iodides such as sodium iodide, potassium iodide and the like; ad mixtures between said Lewis acid and said iodide. The reaction proceeds favorably generally at room temperature to 150°C, preferably at room temperature to 100°C and is complete generally in about 0.5-15 hours. The reaction for converting a compound (In) wherein R 12 is a phenyl-lower alkoxy group, into a compound (lo), can be conducted under the same condi¬ tions as used in the reaction of the compound (5) with the compound (6) by the process (b) (the catalytic reduction process using a catalytic reduction catalyst) in the reaction formula-3. The reaction for converting a compound (In) wherein R 12 is a lower alkanoyloxy group, into a compound (lo), can be conducted under the same conditions as used in the below-mentioned hydrolysis of a compound of general formula (1) wherein R 2 is a phenyl-lower alkyl group having at least one lower-alkoxycarbonyl group as a substituent on the phenyl ring. The reaction of the compound (lo) with the compound (17) can be conducted under the same conditions as used in the reaction of the compound (lc) with the compound (7) in the Reaction formula-4. [Reaction formula-10] (1q) ( r > (wherein, R 1 , R 2 , R 3 and p are the same as defined above; R 1A represents a lower alkylthio-lower alkyl group; and R 13 represents a lower alkylsulfonyl-lower alkyl group) . The reaction for converting a compound (lq) into a compound (lr) is conducted in an appropriate solvent in the presence of an oxidizing agent. The solvent can be exemplified by water, organic acids such as formic acid, acetic acid, trifluoroacetic acid and the like; alcohols such as methanol, ethanol, isopropyl alcohol and the like; halogenated hydrocarbons such as chloroform, dichloromethane and the like; and mixed solvents thereof. The oxidizing agent includes, for example, peracids such as performic acid, peracetic acid, trifluoroperacetic acid, perbenzoic acid, m- chloroperbenzoic acid, o-carboxyperbenzoic acid and the like; hydrogen peroxide; sodium metaperiodate; bichromic acid; bichromates such as sodium bichromate, potassium bichromate and the like; permanganic acid; permanganates such as potassium permanganate, sodium permanganate and the like; and lead salts such as lead tetracetate and the like. The oxidizing agent is used in an amount of generally at least 2 moles, preferably 2-4 moles per mole of the starting material. The reaction is con¬ ducted generally at about 0-40°C, preferably at about 0°C to room temperature and is complete in about 1-15 hours. [Reaction formula-11] (wherein, R 1 , R 2 , R 3 and p are the same as defined above; and R 16 represents a lower alkoxycarbonyl group) . The reduction of the compound (Is) is preferably conducted using a hydride reducing agent. The hydride reducing agent includes, for example, lithium aluminum hydride, sodium borohydride and diborane. The amount of the hydride reducing agent used is at least 1 mole, preferably 1-15 moles per mole of the starting material. The reduction is conducted generally in an appropriate solvent, for example, water, a lower alcohol (e.g. methanol, ethanol, isopropanol or tert-butanol), an ether (e.g. tetrahydrofuran, diethyl ether, diisopropyl ether or diglyme), or a mixed solvent thereof, generally at about -60°C to 150°C, preferably at about -30°C to 100°C for about 10 minutes to 5 hours. When the reducing agent is lithium aluminum hydride or diborane, it is preferable to use an anhydrous solvent such as tetrahydrofuran, diethyl ether, diisopropyl ether, diglyme or the like. [ Reaction formula-12 ] R 18 (1u) (1v) [wherein, R 1 , R 2 and p are the same as defined above; R 17 represents a hydrogen atom, a nitro group, an amino group which may have lower alkanoyl grou(s) as substituent(s) , a halogen atom, a lower alkyl group, a pyrroyl group, a lower alkylthio group, a lower alkanoyl group, a hydroxyl group, an aminocarbonyl group which may have lower alkyl group(s) as substituent(s) , a lower alkoxycarbonyl group, a hydroxyl-substituted lower alkyl group, a phenyl group or a 1,2,4-triazolyl group; R 18 represents an amino group which may have lower alkanoyl group(s) as substituent(s), a pyrroyl group or a 1,2,4- triazolyl group; and X 2 represents a halogen atom]. The reaction of the compound (lu) with the compound (18) can be conducted under the same conditions as used in the reaction of the compound (lc) with the compound (7) in the Reaction formula-4. [Reaction formula-13] (wherein, R 1 , R 2 , R 3 and p are the same as defined above; and R 19 represents a lower alkanoyl group having 1-3 halogen atoms) . The reaction of the compound (lw) with the compound (19) can be conducted under the same conditions as used in the reaction of the compound (2) with the compound (3) in the Reaction formula-1. The reaction for converting a compound (lx) into a compound (ly) can be conducted under the same conditions as used in the reaction of the compound (lc) with the compound (7) in the Reaction formula-4. A compound of general formula (1) wherein R 2 is a phenyl-lower alkyl group having at least one amino group on the phenyl ring, can be converted, by reacting with a compound of general formula (15) : R 10 -OH (15) (wherein, R 10 represents a lower alkanoyl group or a lower alkoxycarbonyl group) or with a compound of general formula (16): R n =N=0 (16) (wherein, R 11 represents a lower alkyl group), into a compound of general formula (1) wherien R 1 or R 2 is a phenyl-lower alkyl group having, on the phenyl ring, at least one amino group having lower alkanoyl group(s), lower alkoxycarbonyl group(s) or aminocarbonyl group(s) each having lower alkyl group(s). The reaction of the starting material with the compound (15) can be conducted under the same conditions as used in the reaction of the compound (2) with the compound (3) in the Reaction formula-1. The reaction of the starting material with the compound (16) can be conducted under the same conditions as used in the reaction of the compound (4) with the compound (3) in the reaction formula-2. A compound of general formula (1) wherein R 2 is a phenyl-lower alkyl group having at least one lower alkoxy group on the phenyl ring, or R 2 form a hetero¬ cyclic ring having at least one lower alkoxy group on the heterocyclic ring, or R 2 is a phenoxy-lower alkyl group having at least one lower alkoxy group on the phenyl ring, can be converted, by dealkylation, into a compound of general formula (1) wherein R 2 is a phenyl- lower alkyl group having at least one hydroxyl group on the phenyl ring, or R 2 form a heterocyclic ring having at least one hydroxyl group on the heterocyclic ring, or R 1 or R 2 is a phenoxy-lower alkyl group having at least one hydroxyl group on the phenyl ring. Said dealkylating reaction can be carried out under the same condition being employed in Reaction formula-9 for obtaining a compound (lo) from a compound (lm). A compound of general formula (1) wherein R 1 or R 2 is a phenyl-lower alkyl group having at least one hydroxyl group on the phenyl ring, or R 1 and R 2 form a heterocyclic ring having at least one hydroxyl group on the heterocyclic ring, or R 2 is a phenoxy-lower alkyl group having at least one hydroxyl group on the phenyl ring, can be converted, by reacting with a compound of general formula (20): R 20 X 2 (20) (wherein, R 20 represents a lower alkyl group and X 2 is the same as defined above), into a compound of general formula (1) wherein R 2 is a phenyl-lower alkyl group having at least one lower alkoxy group on the phenyl ring, or R 1 and R 2 form a heterocyclic ring having at least one lower alkoxy group on the heterocyclic ring. or R 2 is a phenoxy-lower alkyl group having at least one lower alkoxy group on the phenyl ring. The reaction can be conducted under the same conditions as used in the reaction of the compound (lo) with the compound (17) in the Reaction formula-9. A compound of general formula (1) wherein R 2 is a phenyl-lower alkyl group having at least one nitro group on the phenyl ring, or R is a pyridylcarbonyl group having at least one nitro group on the pyridine ring, can be converted, by reduction, into a compound of general formula (1) wherein R 2 is a phenyl-lower alkyl group having at least one amino group on the phenyl ring, or R is a pyridylcarbonyl group having at least one amino group on the pyridine ring. The reduction can be conducted under the same conditions as used in the reduction of the compound (If') in the Reaction formula-8. A compound of general formula (1) wherein R 2 is a phenyl-lower alkyl group having at least one lower alkoxycarbonyl group on te phenyl ring, can be con¬ verted, by hydrolysis, into a compound of general formula (1) wherein R 2 is a phenyl-lower alkyl group having at least one carboxy group on the phenyl ring. The hydrolysis can be carried out in an appropriate solvent or in the absence of any solvent, in the presence of an acid or a basic compound. The solvent includes, for example, water; lower alcohols such as methanol, ethanol, isopropanol and the like; ketones such as acetone, methyl ethyl ketone and the like; ethers such as dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and the like; fatty acids such as formic acid, acetic acid and the like; and mixed solvents thereof. The acid includes, for example, mineral acids such as hydrochloric acid, sulfuric acid, hydrobromic acid and the like; and organic acids such as formic acid, acetic acid, aromatic sulfonic acid and the like. The basic compound includes, for example, metal carbonates such as sodium carbonate, potassium carbonate and the like; and metal hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide and the like. The reaction proceeds favorably generally at about room temperature to 200°C, preferably at about room temperature to 150°C and is complete generally in about 0.5-25 hours. In a compoound (1) , wherein R 1 or R 2 is a phenyl-lower alkyl group having at least one lower alkoxycarbonyl group as substituent on the phenyl ring, such compound can be prepared by esterifying a starting compound (1) , wherein R 1 or R 2 is a phenyl-lower alkyl group having at least one carboxyl group on the phenyl- ring. Said esterification can be conducted by reacting the starting compound (1) , in the presence of a mineral acid for example hydrochloric acid, sulfuric acid or the like; or a halogenating agent for example thionyl chloride, phosphorus oxychloride, phosphorus trichloride, phosphorus pentachloride or the like, with an alcohol for example methanol, ethanol, isopropanol or the like; at temperature of generally from 0 to 150°, preferably at 50 to 100°C, for about 1 to 10 hours. Further the objective esterified compound (1) can be obtained by esterifying the starting compound (1) with a halogenated lower alkyl for example methyl iodide, under the same reaction condition being employed in Reaction formula-4 for reacting a compound (lc) with a compound (7). A compound of general formula (1) wherein R 2 is a phenyl-lower alkyl group having at least one carbamoyl group on the phenyl ring, or R is a benzoyl group having at least one aminocarbonyl group which may have lower alkyl group(s), can be obtained by reacting a compound of general formula (1) wherein R 2 is a phenyl- lower alkyl group having at least one lower alkoxy¬ carbonyl group or at least one carboxy group on the phenyl ring, or R is a benzoyl group having at least one lower alkoxycarbonyl group, with NH 3 or an amine which has lower alkyl group(s), under the same conditions as used in the reaction of the compound (2) with the compound (3) in the Reaction formula-1. A compound of general formula (1) wherein R 2 is a phenyl-lower alkyl group having, on the phenyl ring, at least one amino-lower alkoxy group which may have lower alkyl group(s), or at least one carboxy- substituted lower alkoxy group, can be obtained by reacting a compound of general formula (1) wherein R 2 is a phenyl-lower alkyl group having at least one hydroxyl group on the phenyl ring, with a compound of general formula: R 21 -X x (wherein, R 21 represents an amino-lower alkyl group which may have lower alkyl group(s), or a carboxy-substituted lower alkyl group, and X 1 is the same as defined above) under the same conditions as used in the reaction of the compound (lo) with the compound (17) in the Reaction formula-9. A compound of general formula (1) wherein R 2 is a phenyl-lower alkyl group having at least one lower alkylthio group on the phenyl ring, can be converted, by oxidation under the same conditions as used in the reaction for converting a compound (lq) into a compound (lr) in the reaction formula-10 (the desirable amount of the oxidizing agent used is at least 1 mole, preferably 1-2 moles per mole of the starting material), into a compound of general formula (1) wherein R 2 is a phenyl- lower alkyl group having at least one lower alkyl- sulfinyl group on the phenyl ring. The compound ( 3 ) as starting material can be produced, for example, by the process of the following Reaction formula-14. [Reaction formula-14] (3) (wherein, R 22 represents a phenyl-lower alkyl group, a benzoyl group, or a phenyl-lower alkoxycarbonyl group, and R 1 and R 2 are the same as defined above). The reaction of the compound (21) with the compound (6 ) can be conducted under the same conditions as used in the reaction of the compound (5) with the compound (6) in the reaction formula-3. The reaction for converting a compound (22) wherein R 22 is a phenyl- lower alkyl group or a phenyl-lower alkoxycarbonyl group, into a compound (3) , can be conducted by reduction. The reaction for converting a compound of general formula (1) wherein R 22 is a benzoyl group, into a compound (3) , can be conducted by hydrolysis. The reduction can be conducted under the same conditions as used in the reduction of the compound ( 1. ' ) by the catalytic reduction method (1) in the reaction formula-8 or in the reaction for converting a compound (In) into a compound (lo) in the reaction formula-9. The hydrolysis can be conducted under the same conditions as used in the hydrolysis of a compound of general formula (1) wherein R 1 is a phenyl-lower alkyl group having at least one lower alkoxycarbonyl group on the phenyl ring. A compound of general formula(3) wherein either of R 1 and R 2 is a hydrogen atom, can be converted, by a reaction under the same conditions as used in the reaction formula-4 or 5, into a compound of general formula (3) wherein either of R 1 and R 2 is a group other than hydrogen atom. The compound (2) as a starting material can be produced, for example, by the process of the following reaction formula. [Reaction formula-15] (23) (2) (wherein, Ra is the same as defined above and R 23 represents a lower alkyl group or a phenyl-lower alkyl group) . A compound (23) wherein R 23 is a lower alkyl group, can be converted into a compound (2) by hydrolysis. The hydrolysis can be conducted under the same conditions as used in the hydrolysis of a compound of general formula (1) wherein R 2 is a phenyl-lower alkyl group having at least one lower alkoxycarbonyl group on the phenyl ring. A compound (23) wherein R 23 is a phenyl-lower alkyl group, can be converted into a com¬ pound (2) by reduction. The reduction can be conducted under the same conditions as used in the reduction of the compound ( 1. ' ) by the catalytic reduction method (1) in the Reaction formula-8. A compound of general formula (1) wherein R is a pyridylcarbonyl group having at least one lower alkoxycarbonyl group on the pyridine ring, or a furoyl group having at least one lower alkanoyl group on the furan ring, can be converted, by reduction under the same conditions as used in the reduction of the compound (Is) in the reaction formula-11, into a compound of general formula (1) wherein R is a pyridylcarbonyl group having at least one hydroxymethyl group on the pyridine ring, or a furoyl group having at least one hydroxyl- substituted lower alkyl group on the furan ring. A compound of general formula (1) wherein R 3 is an amino group, can be converted into a compound of general formula (1) wherein R 3 is a cyano group, by reacting the former compound with a metal nitrite (e.g. sodium nitrite or potassium nitrite) in an appropriate solvent and, without isolating the reaction product, reacting said product with a metal cyanide (e.g. copper cyanide) . The solvent can be exemplified by water; alkanoic acids such as acetic acid and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol and the like; halogenated hydrocarbons such as chloroform, dichloromethane, dichloroethane and the like; ethers such as dioxane, tetrahydrofuran and the like; polar solvents such as DMF, DMSO, HMPA and the like; and mixed solvents thereof. The desirable amounts of the metal nitrite and metal cyanide used are each generally at least 1 mole, preferably 1-1.5 moles per mole of the starting material. The reaction proceeds generally at about 0-150°C, preferably at about 0-100°C and is complete generally in about 10 minutes to 5 hours. A compound of general formula (1) wherein R is a furoyl group having at least one nitro group on the furan ring or a thienylcarbonyl group having at least one nitro group on the thiophene ring, can be converted, by reduction under the same conditions as used in the reduction of the compound ( 1. ' ) in the Reaction formula- 8, into a compound of general formula (1) wherein R is a furoyl group having at least one amino group on the furan ring or a thienylcarbonyl group having at least one amino group on the thiophene ring. A compound of general formula (1) wherein R is a furoyl group having at least one amino group on the furan ring or a thienylcarbonyl group having at least one amino group on the thiophene ring, can be converted, by reaction with an agent for introducing a lower alkanoyl group, into a compound of general formula (1) wherein R is a furoyl group having, on the furan ring, at least one amino group having a lower alkanoyl group, or a thienylcarbonyl group having, on the thiophene ring, at least one amino group having a lower alkanoyl group. The agent for introducing a lower alkanoyl group includes, for example, lower alkanoic acids such as formic acid, acetic acid, propionic acid and the like; lower alkanoic acid anhydrides such as acetic anhydride, propionic anhydride and the like; and lower alkanoic acid halides such as acetyl chloride, propionyl bromide and the like. When the agent for introducing a lower alkanoyl group is an acid anhydride or an acid halide, it is possible to allow a basic compound to be present in the reaction system. The basic compound includes, for example, alkali metals such as metallic sodium, metallic potassium and the like; their hydrox- ides, carbonates and bicarbonates; and organic bases such as pyridine, piperidine and the like. The reaction proceeds in the presence or absence of a solvent, but is conducted generally in an appropriate solvent. The solvent includes, for example, ketones such as acetone, methyl ethyl ketone and the like; ethers such as diethyl ether, dioxane and the like, aromatic hydro¬ carbons such as benzene, toluene, xylene and the like; esters such as methyl acetate, ethyl acetate and the like; acetic acid; acetic anhydride; water; and pyridine. The desirable amount of the agent for introducing a lower alkanoyl group is at least about equimolar, generally equimolar to a large excess over the starting material. The reaction favoraly proceeds generally at about 0-150°C, preferably at about 0-100°C and is complete generally in about 5 mintes to 24 hours. When the agent for introducing a lower alkanoyl group is a lower alkanoic acid, it is desirable to add to the reaction system a dehydrating agent such as mineral acid (e.g. sulfuric acid or hydrochloric acid), sulfonic acid (e.g. p-toluenesulfonic acid, benzenesulfonic acid or ethanesulfonic acid) or the like. The reaction temperature is particularly preferably about 50-120°C. A compound of general formula (1) wherein R is a formyl group, can be obtained by reacting a compound of general formula (3) : with a di-lower alkylformaldehyde such as dimethylform- aldehyde or the like. The desirable amount of the di- lower alkylformaldehyde used is generally a large excess over the compound (3) . The reaction is conducted generally at about room temperature to 200°C, preferably at about room temperature to 150°C and is complete in about 1-30 hours. A compound of general formmula (1) wherein R is a group of the formula: (wherein, W, Y, Z and the dotted line in -W are the same : :l / Y as defined above) and said group has at least one lower alkylthio group thereon, can be converted, by desulfuri- zation, into a compound of general formmula (1) wherein R is a group of the formula: (wherein, W, Y, Z and the dotted line in -W are the same il /Y as defined above) and said may have thereon at least one lower alkylthio group, the number of said at least one alkylthio group being smaller by at least one than the number of the at least one alkylthio group of the compound before desulfurization. The desulfurization is conducted generally in the presence of an appropriate catalyst in a solvent. The catalyst can be exemplified by aluminum amalgum, lithium-lower alkylamine, Raney nickel, Raney cobalt, triethyl phosphite and triphenylphosphine. Raney nickel is preferable. The solvent can be exemplified by alcohols such as methanol, ethanol, isopropanol and the like, and ethers such as dioxane, tetrahydrofuran, diethyl ether and the like. The reaction is conducted at about 0-200°C, preferably at about room temperature to 100°C and is complete in about 10 minutes to 5 hours. A compound of general formula (1) wherein R is a group of the formula: (wherein, W, Y, Z and the dotted line in -W are the same as defined above) and said group has at least one halogen atom thereon, can be converted, by dehalogena- tion, into a compound of general formmula (1) wherein R is a group of the formula: (wherein, W, Y, Z and the dotted line in -W are the same II / γ as defined above) and said group may have thereon at least one halogen atom, the number of said at least one halogen atom being smaller by at least one than the number of the at least one halogen atom of the compound before dehalogenation. The dehalogenation can be conducted under the same conditions as used in the reduction of the compound ( 1. ' ) by the method using a catalytic reduction catalyst in the Reaction formula-8. The dehalogenation favorably proceeds when a basic compound such as triethylamine or the like is added. The compound (23) as starting material can be produced, for example, by the processes of the following reaction formulas. [Reaction formula-16] < 24 > (23a) (wherein, R 3 , R 23 , p and X 2 are the same as defined above; and R 2 represents a 1,2,4-triazolyl group which may have oxo group(s) on the 1,2,4-triazole ring, a 1,2,3,4-tetrazolyl group, an imidazolidinyl group which may have 1-2 substituents selected from the group consisting of a phenyl group and a lower alkyl group, on the imidazole ring, a pyrazolyl group which may have lower alkyl group(s) on the pyrazole ring, a pyrrolyl group, a pyrrolidinyl group which may have oxo group(s) on the pyrrolidine ring, a piperidinyl group which may have oxo group(s) on the piperidine ring, an benzoim- idazolyl group, an imidazolidinyl group which may have oxo group(s) on the imidazolidine ring, or a 2-oxazolid- inyl group) . The reaction of the compound (24) with the compound (25) can be conducted under the same conditions as used in the reaction of the compound (lc) with the compound (7) in the reaction formula-4. [Reaction formula-17] (wherein, R 3 R 23 and p are the same as defined above) . The reaction for converting a compound (26) into a compound (27) can be conducted by reacting the compound (26) with an acid (e.g. sulfuric acid, hydro¬ chloric acid, hydrobromic acid or fluoroboric acid) and sodium nitrite in a solvent such as lower alkanoic acid (e.g. acetic acid), water or the like to form a diazo- nium salt and then reacting the diazonium salt with sulfurous acid or a metal salt (e.g. sodium hydrogen- sulfite or stannous chloride) in a solvent such as water or the like. The desirable amount of sodium nitrite used is generally 1-2 moles, preferably 1-1.5 moles per mole of the compound (26). The desirable reaction temperature is generally about -20°C to room temperature, preferably about -5°C to room temperature, and the reaction time is generally about 5 minutes to 5 hours. In the subsequent reaction of the diazonium salt with sulfurous acid, the desirable reaction temper¬ ature is generally about 0-150°C, preferably about 0- 100°C, and the reaction time is generally about 1-50 hours. The reaction for converting the compound (27) into a compound (23b) can be conducted by reacting the compound (27) with 1,3,5-triazine in an appropriate solvent. The solvent can be any solvent mentioned with respect to the reaction of the compound (5) with the compound (6) in the reaction formula-3. The reaction is desirably conducted generally at about room temperature to 150°C, preferably at about room temperature to 100°C and is complete generally in about 1-10 hours. The amount of 1,3,5-triazine used is generally 0.1-5 moles, preferably 0.1-2 moles per mole of the compound (27) . The reaction of the compound (27) with a compound (28) can be conducted in an appropriate solvent in the presence of an acid or a basic compound. The solvent includes, for example, water; alcohols such as methanol, ethanol, isopropanol and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; and aprotic polar solvents such as dimethyl- formamide, dimethylacetamide, N-methylpyrrolidone and the like. The acid includes, for example, mineral acids such as hydrochloric acid, sulfuric acid, boron tri¬ fluoride and the like; and organic acids such as p- toluenesulfonic acid and the like. The basic compound can be exemplified by inorganic bases such as potassium carbonate, sodium carbonate, potassium hydrogen¬ carbonate, sodium hydrogencarbonate and the like, and organic bases such as sodium acetate and the like. The desirable amount of the compound (28) used is at least 1 mole, preferably 1-2 moles per mole of the compound (27). The desirable amount of the acid or basic com¬ pound used is at least 1 mole, preferably 1-5 moles per mole of the compound (27). The reaction is conducted generally at about room temperature to 150°C, preferably at about room temperature to 100°C and is complete in about 5 minutes to 5 hours. The subsequent cyclization can be conducted by reaction with diphenyl phosphoryl azide in the above- mentioned solvent in the presence of an appropriate basic compound. The basic compound can be any basic compound used in the reaction of the compound (lc) with the compound (7) in the reaction formula-4. The desira¬ ble amount of diphenyl phosphoryl azide used is at least 1 mole, preferably 1-2 moles per mole of the compound (27). The reaction is conducted generally at about room temperature to 200°C, preferably at about 50-150°C and is complete in about 1-10 hours. [Reaction formula-18] (29) (23d) (wherein, R 3 , R 23 and p are the same as defined above). The halogenation of the compound (29) can be conducted under the same conditions as used in the reaction for production of a carboxylic acid halide in the reaction formula-1. The subsequent cyclization can be conducted in an appropriate solvent in the presence of a basic compound. The solvent and basic compound can be each any of those mentioned with respect to the reaction of the compound (lc) with the compound (7) in the reaction formula-4. The cyclization is conducted generally at about 0-70°C, preferably at about 0°C to room temperature and is complete in about 5 minutes to 5 hours. [ Reaction formula-19 ] R 26 -H ( 31 ) X 2 -A-C0 2 -R 25 • > R 26 -A-C0 2 -R 25 ( 30 ) ( 23e ) [wherein, X 2 is the same as defined above; A represents a lower alkylene group; R 25 represents a phenyl-lower alkyl group; and R 26 represents a 1,2,4-triazolyl group or an amino group which may have lower alkyl group(s)]. The lower alkylene group can be exemplified by C 1 " 6 straight- or branched-chain alkylene group such as methylene, ethylene, trimethylene, 2-methyltrimethylene, 2,2-dimethyltrimethylene , 1-methyltrimethylene, methylmethylene, ethylmethylene, tetramethylene, pentamethylene, hexamethylene and the like. The reaction of the compound (30) with the compound (31) can be conducted under the same conditions as used in the reaction of the compound (lc) with the compound (7) in the Reaction formula-4. [Reaction formula-20 ] ( 1Z ) ( 1A) (wherein, R 1 , R 2 , R 3 and p are the same as defined above; and R 29 and R 30 , which may be the same or different, each represent a hydrogen atom, a lower alkyl group or a phenyl group) . The reaction of the compound (lz) with the compound (32) can be conducted under the same conditions as used in the reaction of the compound (2) with the compound (3) in the Reaction formula-1. [Reaction formula-21] R b CHO (33) (3) (IB) [wherein, R 1 and R 2 are the same as defined above; and R b represents a group of the formula: (R 3 and m are the same as defined above); a lower alkyl group which may have hydroxyl group(s) or amino group(s) which may each have lower alkyl group(s); a lower alkyl group having 1-3 halogen atoms; a pyridyl group which may have, on the pyridine ring, substituent(s) selected from the group consisting of a nitro group, an amino group which may have lower alkanoyl group(s) as substi- tuent(s), a halogen atom, a lower alkyl group, a pyrro¬ lyl group, a lower alkylthio group, a lower alkanoyl group, a hydroxyl group, an aminocarbonyl group which may have lower alkyl group(s) as substituent(s) , a lower alkoxycarbonyl group, a hydroxyl-substituted lower alkyl group, a phenyl group and a 1,2,4-triazolyl group; a 1,2,4-triazolyl-lower alkyl group; a furyl group which may have, on the furan ring, substituent(s) selected from the group consisting of a nitro group, a hydroxyl- substituted lower alkyl group, a lower alkanoyl group and an amino group which may have lower alkanoyl group(s); a thienyl group which may have, on the thio- phene ring, substituent(s) selected from the group consisting of a nitro group, a lower alkyl group, a halogen atom and an amino group which may have lower alkanoyl group(s); a fluorenyl group which may have, on the fluorene ring, substituent(s) selected from the group consisting of an oxo group and a nitro group; or a group of the formula: (wherein, Y, W, Z, the dotted line in the bond -W and A the substituent on the group are the same as mentioned above)]. The reaction of the compound (33) with the compound (3) can be conducted by reaction with a metal cyanide (e.g. sodium cyanide) and subsequent reaction with an oxidizing agent both in an appropriate solvent. The solvent can be any solvent used in the reaction for converting a compound (lq) into a compound (lr) in the reaction formula-10. The oxidizing agent can be manganese dioxide or any oxidizing agent used in the reaction for converting the compound (lq) into the compound (lr) in the Reaction formula-10. The desirable amount of the metal cyanide used is at least 1 mole, preferably 1-10 moles per mole of the compound (33). The desirable amount of the oxidiz¬ ing agent used is generally a large excess over the compound (33). The desirable amount of the compound (3) is at least 1 mole, preferably 1-2 moles per mole of the compound (33). The reaction with the metal cyanide and the reaction with the oxidizing agent are conducted generally at about 0-40°C, preferably at about 0°C to room temperature and is complete in about few minutes to 5 hours. [Reaction formula-22] (1C) (ID) [wherein, R and R la are the same as defined above; R ld represents a phthalimido-substituted lower alkyl group; and R le represents a group of the formula: -B-NH 2 (wherein, B is the same as defined above)]. The reaction for converting a compound (1C) into a compound (ID) can be carried out by reacting the compound (1C) with hydrazine in an appropriate solvent or by hydrolysis of the compound (1C). As to the solvent to be used in the rection of the compound (1C) with hydrazine, there can be exemplified by water; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as tetrahydrofuran, dioxane, diethyl ether, diethylene glycol dimethyl ether and the like; alcohols such as methanol, isopropanol, butanol and the like; acetic acid; and inert solvents such as ethyl acetate, acetone, acetonitrile, dimethylformamide, dimethyl sulfoxide, hexamethylphosphoric triamide and the like. The reaction is conducted generally at about room temperature to 120°C, preferably at about 0-100°C and is complete generally in about 5 minutes to 5 hours. The desirable amount of hydrazine used is at least about - I l l - 1 mole, preferably about 1-5 moles per mole of the compound (1C) . The hydrolysis can be conducted under the same conditions as used in the above-mentioned hydrolysis of a compound of general formula (1) wherein R 2 is a phenyl-lower alkyl group having at least one lower alkoxycarbonyl group on the phenyl ring. [Reaction formula-23] (wherein, R, R la , R 8 , R 9 , R 27 , B and X x are the same as defined above; R 28a represents a lower alkanoyl group or a benzoyl group; and R 28b represents a lower alkyl group) . The reaction of the compound (IE) with the compound (34) can be conducted under the same conditions as used in the reaction of the compound (2) with the compound (3) in the reaction formula-1. The reaction of the compound (IE) with the compound (35) can be conducted under the same conditions as used in the reaction of the compound (lc) with the compound (7) in the reaction formula-4. The reaction of the compound (IE) with the compound (9) can be conducted under the same conditions as used in the reaction of the compound (lc) with the compound (9) in the reaction formula-5. The piperidine derivatives represented by general formula (1) according to the present invention can each form an acid addition salt easily by being reacted with a pharmacologically acceptable acid. The acid can be exemplified by inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid and the like, and organic acids such as oxalic acid, maleic acid, fumaric acid, malic acid, tartaric acid, citric acid, benzoic acid and the like. Of the present piperidine derivatives represented by general formula (1), those having an acidic group can each form a salt easily by being reacted with a pharma¬ cologically acceptable basic compound. The basic com¬ pound can be exemplified by sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate and potassium hydrogencarbonate. Each of the intended compounds obtained by the above reaction formulas can be easily separated from the reaction system and purified by ordinary means. The means for separation can be exemplified by solvent extraction, dilution, recrystallization, column chroma¬ tography and preparative thin-layer chromatography. Needless to say, the present piperidine derivatives of general formula (1) include optical isomers. Each of the compounds of general formula (1) is used generally in the form of ordinary pharmaceutical preparation. The pharmaceutical preparation is prepared by using diluents or excipients ordinarily used, such as filler, bulking agent, binder, humectant, disintegrator, surfactant, lubricant and the like. The pharmaceutical preparation can be prepared in various forms depending upon the purpose of remedy, and the typical forms include tablets, pills, a powder, a solution, a suspension, an emulsion, granules, an ointment, suppositories, an injection (e.g. solution or suspen¬ sion), etc. In preparing tablets, there can be used various carriers exemplified by excipients such as lactose, white sugar, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystalline cel¬ lulose, silicic acid and the like; binders such as water, ethanol, propanol, simple syrup, lactose solu- tion, starch solution, gelatin solution, carboxymethyl cellulose, shellac, methyl cellulose, potassium phos¬ phate, polyvmylpyrrolidone and the like; disintegrators such as dry starch, sodium alginate, powdered agar, powdered laminarin, sodium hydrogencarbonate, calcium carbonate, polyoxyethylene sorbitan-fatty acid esters, sodium lauryl sulfate, stearic acid monoglyceride, starch, lactose and the like; disintegration inhibitors such as white sugar, stearin, cacao butter, hydrogenated oil and the like; absorption promoters such as quater- nary ammonium salts, sodium lauryl sulfate and the like; humectants such as glycerine, starch and the like; adsorbents such as starch, lactose, kaolin, bentonite, colloidal silicic acid and the like; and lubricants such as refined talc, stearic acid salts, boric acid powder, polyethylene glycol and the like. The tablets can be prepared, as necessary, in the form of ordinary coated tablets, such as sugar-coated tablets, gelatin-coated tablets, enteric coated tablets or film-coated tablets, or in the form of double-layered tablets or multi- layered tablets. In preparing pills, there can be used various carriers exemplified by excipients such as glucose, lactose, starch, cacao butter, hardened vegeta- ble oils, kaolin, talc and the like; binders such as powdered acacia, powdered tragacanth, gelatin, ethanol and the like; and disintegrators such as laminarin, agar and the like. In preparing suppositories, there can be used carriers exemplified by a polyethylene glycol, cacao butter, a higher alcohol, a higher alcohol ester, gelatin and a semi-synthetic glyceride. Capsules can be prepared generally by mixing the present compound with various carriers mentioned above and filling the mixture into a hard gelatin capsule or a soft capsule according to an ordinary method. In preparing an injection (solution, emulsion or suspension), it is sterilized and is preferably made isotonic to the blood. In preparing the solution, emulsion or suspension, there can be used diluents such as water, ethyl alcohol, polyethylene glycol, propylene glycol, ethoxylated isostearyl alco¬ hol, polyoxy-isostearyl alcohol and polyoxyethylene sorbitan-fatty acid esters. In this case, the injection may contain sodium chloride, glucose or glycerine in an amount sufficient to make the injection isotonic, and may further contain a solubilizing agent, a buffer solution, a soothing agent, etc. all ordinarily used. The pharmaceutical preparation may furthermore contain, as necessary, a coloring agent, a preservative, a perfume, a flavoring agent, a sweetening agent and other drugs. In preparing the present pharmaceutical prepara¬ tion in the form of a paste, a cream or a gel, there can be used diluents such as white petrolatum, paraffin, glycerin, cellulose derivatives, polyethylene glycol, silicon, bentonite and the like. The amount of the present compound to be contained in the pharmaceutical preparation of the present invention is not particularly restricted and can be appropriately selected from a wide range, but the desirable amount is generally 1-70% by weight, prefer¬ ably 1-30% by weight in the pharmaceutical preparation. The method for administering the pharma¬ ceutical preparation is not particularly restricted. It is decided depending upon the form of preparation, the age, distinction of sex and other conditions of patient, the disease condition of patient, etc. For example, tablets, pills, a solution, a suspension, an emulsion, granules or capsules are administered orally. An injection is intravenously administered singly or in admixture with an ordinary auxiliary solution of glucose, amino acids or the like, or, as necessary, is singly administered intramuscularly, intradermally, subcutaneously or intraperitoneally. Suppositories are administered intrarectally. The dose of the pharmaceutical preparation is appropriately selected depending upon the administration method, the age, distinction of sex and other conditions of patient, the disease condition of patient, etc., but the desirable dose is generally about 0.01-10 mg per kg of body weight per day in terms of the amount of the active ingredient, i.e. the present compound of general formula (1). The desirable content of the active ingredient in each unit of administration form is 0.1- 200 mg. [Examples] The present invention is described more specifically below with reference to Preparation Examples, Reference Examples, Examples and Pharmacological Test. Preparation Example 1 4-[N-methyl-N-(2-phenylethyl)amino]-l-[3-(2- dimethyaminoethoxy)-4-(1,2,4-triazol-l-yl)- benzoyl]piperidine 5 mg Starch 132 mg Magnesium stearate 18 mg Lactose 45 mσ Total 200 mg Tablets each containing the above components in the above amounts were prepared according to an ordianry method. Preparation Example 2 4-[N-methyl-N-(2-phenylethyl)amino]-l-[3-(2- dimethylaminoethoxy)-4-(1,2,4-triazol-l-yl)- benzoyl]piperidine 500 mg Polyethylene glycol (molecular weight: 4000) 0.3 g Sodium chloride 0.9 g Polyoxyethylene sorbitan mono-oleate 0.4 g Sodium metabisulfite 0.1 g Methylparaben 0.18 g Propylparaben 0.02 g Distilled water for injection 100 ml The above parabens, sodium metabisulfite and sodium chloride were dissolved in the above distilled water at 80°C with stirring. The resulting solution was cooled to 40°C. Therein were dissolved the above compound (present compound), polyethylene glycol and polyoxyethylene sorbitan mono-oleate in this order. To the resulting solution was added the above distilled water to obtain a final volume, followed by filtration through an appropriate filter paper for sterilization. The sterile filtrate was poured into vials each in an amount of 1 ml to prepare an injection. Reference Example 1 2 g of p-toluenesulfonic acid was added to a solution of 230 g of 4-oxo-l-benzylpiperidine and 221 g of 2-phenethylamine in 1 liter of toluene. The mixture was refluxed for 1 hour while removing the generated water using a Dean-Stark trap. The reaction mixture was concentrated under reduced pressure. To the residue was added 1 liter of ethanol. To the mixture being ice- cooled was slowly added 22 g of sodium boron hydride. The resulting mixture was stirred at room temperature for 4 hours. The reaction mixture was ice-cooled, and then was made acidic by slow addition of concentrated hydrochloric acid. The resulting crystals were collected by filtration. The crystals were dissolved in water. The solution was made alkaline with a 25% aqueous sodium hydroxide solution and then extracted with methylene chloride. The extract was water-washed, dried with anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 222.2 g of 4-(2- phenylethylamino)-l-benzylpiperidine as a light yellow oily substance. X H-NMR (200 MHz, CDC1 3 ) S ppm: 1.20-1.75 (3H, m) , 1.75-1.90 (2H, ), 1.90-2.10 (2H, m) , 2.37-2.58 (IH, m), 2.70-3.00 (6H, m) , 3.48 (2H, ), 7.12-7.45 (10H, m) Reference Example 2 136 ml of formic acid was added to 210 g of 4- (2-phenylethylamino)-l-benzylpiperidine. Since the temperature of the mixture increased to about 90°C, the mixture was ice-cooled. To the reaction mixture was added 64 ml of 37% formalin at 50-60°C; the ice bath was removed; and the mixture was stirred for 1 hour. To the resulting reaction mixture were added 1 liter of ethanol and 120 ml of concentrated hydrochloric acid, followed by concentration under reduced pressure. To the residue was added 1 liter of ethanol. The resulting insolubles were collected by filtration and then washed with ethanol to obtain 251.7 g of 4-[N-methyl-N-(2- phenylethyl)amino]-l-benzylpiperidine dihydrochloride as a white powder. X H-NMR (200 MHz, D 2 0) δ ppm: 1.88-2.20 (2H, ) , 2.20-2.43 (2H, m) , 2.90 (3H, s), 3.00-3.25 (4H, m) , 3.37-3.56 (2H, m), 3.56-3.81 (3H, m), 4.33 (2H, s), 7.25-7.54 (5H, m) , 7.54-7.60 (5H, m) Reference Example 3 60 ml of concentrated hydrochloric acid and 13.3 g of 10% palladium-carbon were added to a solution of 266 g of 4-[N-methyl-N-(2-phenylethyl)amino]-l- benzylpiperidine in 1 liter of ethanol and 500 ml of water. The mixture was stirred at a hydrogen pressure of 1 atm. at 60°C for 5 hours. 10% palladium-carbon was removed by filtration and then washed with ethanol. The filtrate and the washings were combined and concentrated under reduced pressure. The residue was added to ice water. The mixture was made alkaline with a 25% aqueous sodium hydroxide solution and then extracted with methylene chloride. The extract was water-washed and then concentrated under reduced pressure. The residue was subjected to vacuum distillation to obtain 131.9 g of 4-[N-methyl-N-(2-phenylethyl)amino]piperidine as a colorless oil. Boiling point: 137-139°C/0.2 mmHg Reference Example 4 60 ml of 5 N hydrochloric acid was added to a solution of 5.8 g of 4-{N-methyl-N-[2-(4-methylthio¬ phenyl)ethyl]amino}-1-benzoylpiperidine in 20 ml of ethanol. The mixture was refluxed by heating, for 12 hours. To the reaction mixture was added 100 ml of ethanol, followed by concentration under reduced pressure. To the residue was added ice water. The mixture was made basic with a 25% aqueous sodium hydroxide solution and then extracted with chloroform. The extract was water-washed, dried with anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 3.7 g of 4-{N-methyl-N-[2-(4-methylthio¬ phenyl)ethyl]amino}piperidine as a light yellow oily substance. Reference Example 5 A suspension of 16.4 g of ethyl 4-fluoro- benzoate, 20 g of triazole and 20 g of potassium carbonate in 50 ml of dimethyl sulfoxide was stirred in a nitrogen atmosphere at 130°C for 1.5 hours. The reaction mixture was poured into ice water. The mixture was extracted with ethyl acetate. The extract was water-washed, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluant: methylene chloride/methanol = 100/1 to 50/1). The former eluate portion was subjected to crystallization with diisopropyl ether. The resulting crystals were recrystallized from ethanol-water to obtain 3.1 g of ethyl 4-(l,2,4-triazol-l-yl)benzoate as colorless needle-like crystals. Melting point: 97-99°C The latter eluate portion was subjected to precipitation with diethyl ether. The precipitate was collected by filtration to obtain 1.3 g of ethyl 4- (l,2,4-triazol-4-yl)benzoate as a white powder. Melting point: 209-211°C. Reference Example 6 5.5 ml of a 5 N aqueous sodium hydroxide solution was added to a solution of 1.2 g of ethyl 4- (l,2,4-triazol-4-yl)benzoate in 15 ml of ethanol. The mixture was stirred at 50-60°C for 1 hour. The reaction mixture was concentrated under reduced pressure. To the residue was added ice water. The mixture was made acidic with acetic acid. The resulting crystals were collected by filtration, water-washed, and dried to obtain 0.95 g of 4-(l,2,4-triazol-4-yl)benzoic acid as a white powder. Melting point: 300°C or above tø-NMR (250 MHz, DMS0-d 6 ) δ ppm: 7.87 (2H, d, J=8.5 Hz), 8.09 (2H, d, J=8.5 Hz), 9.24 (2H, s), 13.21 (IH, brs) Reference Example 7 A solution of 5.75 g of sodium nitrite in 30 ml of water was dropwise added to a solution of 11.7 g of methyl 3-aminobenzoate and 20 ml of concentrated hydrochloric acid in 200 ml of water, at about 0°C with cooling with ice-methanol. The mixture was stirred at the same temperature for 5 minutes. The mixture was then added to 650 ml of a 6% aqueous sulfurous acid solution being ice-cooled. The resulting mixture was stirred at 50-60°C for 2 days. The reaction mixture was allowed to cool and then extracted with ethyl acetate. The aqueous layer was made basic with an aqueous sodium hydroxide solution and extracted with ethyl acetate. The extract was washed with water and an aqueous sodium chloride solution in this order, then dried with anhydrous sodium sulfate, and concentrated under reduced pressure. To the residue was added ethanol. The mixture was made acidic with concentrated hydrochloric acid and then concentrated under reduced pressure. To the residue was added a slight amount of ethanol. The resulting insolubles were collected by filtration. washed with ethanol, and dried to obtain 3.1 g of methyl 3-hydrazinobenzoate hydrochloride as a white powder. Melting point: 184.5-185.5°C Reference Example 8 1.04 g of 1,3,5-triazine was added to a solution of 3.7 g of methyl 3-hydrazinobenzoate hydrochloride in 20 ml of ethanol. The mixture was refluxed by heating, for 3 hours. The reaction mixture was allowed to cool and mixed with chloroform. The resulting insolubles were removed by filtration. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluant: methylene chloride/methanol = 100/0 to 100/1) and then subjected to crystallization from diisopropyl ether. The crystals were collected by filtration to obtain 2.0 g of methyl 3-(l,2,4-triazol-l-yl)benzoate as colorless needle-like crystals. Melting point: 115-120°C Reference Example 9 5.6 ml of concentrated hydrochloric acid was added to a suspension of 7.5 g of methyl 4-hydrazino- benzoate in 150 ml of water. Thereto was dropwise added a solution of 4.6 g of glyoxylic acid in 20 ml of water. The mixture was stirred for 10 minutes. The resulting crude crystals were collected by filtration, water- washed, and suspended in 150 ml of toluene. The suspension was concentrated under reduced pressure. This procedure was repeated again and the resulting concentrate was dried. The concentrate was suspended in 150 ml of toluene. To the suspension were added 6.3 ml of triethylamine and 9.7 ml of diphenyl phosphoryl azide in this order. The mixture was refluxed for 1 hour and then allowed to cool. The resulting insolubles were collected by filtration, washed with ethyl acetate, and recrystallized from methanol to obtain 4.3 g of methyl 4-(5-oxo-l,2,4-triazol-l-yl)benzoate as orange needle¬ like crystals. tø-NMR (200 MHz, DMS0-d 6 ) δ ppm: 3.85 (3H, s), 8.05 (2H, d, J=9.2 Hz), 8.07 (2H, d, J=9.2 Hz), 8.20 (IH, s), 12.12 (IH, brs) Reference Example 10 2.2 ml of thionyl chloride was added to 2.23 g of methyl 4-(2-hydroxyethyl)aminocarbonylbenzoate. The mixture was stirred for 15 minutes. Thereto was added 10 ml of diethyl ether. The reaction mixture was added to 20 ml of a 5 N aqueous sodium hydroxide solution being cooled with an ice-methanol cryogen. The mixture was stirred for a while. The resulting precipitate was collected by filtration and water-washed to obtain a white powder. The powder was dissolved in 20 ml of methanol. Thereto was added 4 ml of 5 N sodium hydroxide. The mixture was stirred at 40°C for 15 minutes and then concentrated under reduced pressure. To the residue was added ice water. The mixture was made acidic with acetic acid. The resulting crystals were collected by filtration, washed with water and methanol in this order, and dried to obtain 1.6 g of 4- (2-oxazolin-2-yl)benzoic acid as a white powder. Melting point: 300°C or above -NMR (200 MHz, DMSO-d 6 ) δ ppm: 3.99 (2H, t, J=9.4 Hz), 4.43 (2H, t, J=9.4 Hz), 7.97 (2H, d, J=8.6 Hz), 8.02 (2H, d, J=8.6 Hz), 13.22 (IH, s) Reference Example 11 4.7 g of 1,2,4-triazole and 9.5 g of potassium carbonate were added to a solution of 15 g of benzyl 4- bromobutyrate in 150 ml of acetonitrile. The mixture was refluxed by heating, for 1 hour. The reaction mixture was concentrated under reduced pressure. To the residue was added 30 ml of methylene chloride. The insolubles were collected by filtration and washed. The filtrate and the washings were combined and purified by silica gel column chromatography (eluant: methylene chloride/methanol = 50/1) to obtain 11.6 g of benzyl 4- (l,2,4-triazol-l-yl)butyrate as a colorless oily substance. ^-NMR (200 MHz, CDC1 3 ) δ ppm: 2.14-2.32 (2H, m), 2.32-2.44 (2H, ), 4.24 (2H, t, J=6.7 Hz), 5.13 (2H, s), 7.30-7.45 (5H, m) , 7.94 (IH, s), 8.00 (IH, s) Reference Example 12 0.5 g of 5% palladium carbon was added to a solution of 11 g of benzyl 4-(1,2,4-triazol-l-yl)butyr- ate in 150 ml of ethanol. The mixture was stirred at a hydrogen pressure of 1 atm. at room temperature for 1 hour. Thereto was added 100 ml of ethanol. The mixture was heated and made uniform. Palladium carbon was collected by filtration and washed with ethanol. The filtrate and the washings were combined and concentrated under reduced pressure. To the residue was added a small amount of ethanol. The resulting insolubles were collected by filtration to obtain 6.2 g of 4-(l,2,4- triazol-1-yl)butyric acid as a white powder. X H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.98 (2H, quint, J=6.8 Hz), 2.21 (2H, t, J=6.8 Hz), 4.20 (2H, t, J=6.8 Hz), 7.96 (IH, s), 8.50 (IH, s), 12.19 (IH, s) Reference Examples 13-28 Using suitable starting materials, the compounds shown in Table 1 were obtained in the same manner as in Reference Example 3 or 4. [Table 1 ] CTable 1 (Continued)] C Table 1 (Continued)!) Table 1 (Continued)] Table 1 (Continued)] CTable 1 (continued)] Reference Example 27 Structural formula: Crystal form: white powder Melting point (°): 250 or above (decompd. Salt form: dihydrochloride NMR value: 14 ) Reference Example 28 Structural formula: Crystal form: light orange oil Salt form: free NMR value: 15) Reference Examples 29 - 40 By the method similar to that of employed in Reference Example 5, and by using suitable starting materials, there were prepared compounds of Reference Examples 29 - 40 as shown in the following Table 2. [Table 2] Ra-OR 23 Reference Example 29 Structural formula: Crystal form: white powder Salt form: free NMR value: 16) Reference Example 30 Structural formula: Crystal form: light yellow needles Recrystallization solvent: ethyl acetate-n-hexane Melting point (°C): 126-129 Salt form: free C Table 2 ( cont inued ) ] Reference Example 31 Structural formula: >23 CH. Crystal form: light red prisms Melting point (°C): 105-107 Salt form: free Reference Example 32 Structural formula: Crystal form: white powder Salt form: free NMR value: 17 ) J . able 2 (continued)] Reference Example 34 Structural formula: Crystal form: colorless oil Salt form: free NMR value: 19) Reference Example 35 Structural formula: Crystal form: colorless needles Recrystallization solvent: methanol-water Melting point (°C): 99.5-100.5 Salt form: free Reference Example 36 Structural formula: R 23 : CH 3 Crystal form: colorless needles Melting point (°C): 135.5-137.5 Salt form: free CTable 2 (continued)] Reference Example 37 Structural formula: Crystal form: colorless needles Recrystallization solvent: ethanol Melting point (°C): 134-136 Salt form: free Reference Example 38 Structural formula: Crystal form: colorless scales Recrystallization solvent: ethanol Melting point (°C): 108-110 Salt form: free CTable 2 (continued)] Reference Example 39 Structural formula: Crystal form: colorless needles Recrystallization solvent: ethanol Melting point (°C): 201-202.5 Salt form: free Reference Example 40 Structural formula: Crystal form: colorless prisms Melting point (°C): 163-164.5 Salt form: free Reference Examples 41 - 73 By the method similar to that of employed in Reference Example 6 or 12, and by using suitable starting materials, there were prepared compounds of Reference Examples 41 - 73 as shown in the following Table 3. [Table 3] Ra-OH Reference Example 41 Structural formula: Crystal form: white powder Salt form: free NMR value: 20) Reference Example 42 Structural formula: Crystal form: white powder Melting point ( β C): 300 or above Salt form: free NMR value: 21) Reference Example 43 Structural formula: Crystal form: white powder Salt form: free NMR value: 22 ) J.Table 3 (continued)] Reference Example 44 Structural formula: Crystal form: white powder Melting point (°C): 224-231 Salt form: free NMR value: 23) Reference Example 45 Structural formula: Crystal form: light red powder Melting point (°C): 268-271 Salt form: free Reference Example 46 Structural formula: Ra NO 2 Crystal form: light yellow powder Melting point (°C): 278-279 Salt form: free Table 3 (continued)] Reference Example 47 Structural formula: Crystal form: white powder Salt form: free NMR value: 24 ) Reference Example 48 Structural formula: Crystal form: white powder Salt form: free NMR value: 25) Reference Example 49 Structural formula: Crystal form: light red needles Salt form: free NMR value: 26 ) (Table 3 (continued)] Reference Example 50 Structural formula: Crystal form: light brown powder Salt form: free NMR value: 27 ) Reference Example 51 Structural formula: Crystal form: colorless needles Melting point (°C): 277 ■279 ( decompd. ) Salt form: free Reference Example 52 Structural formula: Crystal form: white powder Melting point (°C): 260-267 Salt form: free NMR value: 28 ) (Table 3 (continued)] Reference Example 53 Structural formula: Crystal form: colorless needles Salt form: free NMR value: 29 ) Reference Example 54 Structural formula: Crystal form: white powder Salt form: free NMR value: 30) Reference Example 55 Structural formula: Crystal form: light yellow powder Melting point (°C): 261-263 (decompd.) Salt form: free (Table 3 (continued)] Reference Example 56 Structural formula: Crystal form: white powder Salt form: free NMR value: 31 ) Reference Example 57 Structural formula: Crystal form: white powder Salt form: free NMR value: 32 ) Reference Example 58 Structural formula: Crystal form: white powder Salt form: free NMR value: 33) (Table 3 (continued)] Reference Example 59 Structural formula: Crystal form: white powder Salt form: free NMR value: 34 ) Reference Example 60 Structural formula: Crystal form: white powder Salt form: free NMR value: 35) Reference Example 61 Structural formula: Crystal form: white powder Salt form: free NMR value: 36) (Table 3 (continued)] Reference Example 62 Structural formula: Reference Example 63 Structural formula : Crystal form: light yellow powder Salt form: free NMR value: 37) Reference Example 64 Structural formula: Crystal form: light yellow powder Salt form: free NMR value: 38) (Table 3 (continued)] Reference Example 65 Structural formula: Crystal form: white powder Melting point (°C): 300 or above Salt form: free NMR value: 39) Reference Example 66 Structural formula: Crystal form: white powder Melting point (°C): 300 or above Salt form: free NMR value: 40) Reference Example 67 Structural formula: Crystal form: white powder Salt form: free NMR value: 41 ) (.Table 3 ( continued ) ] Reference Example 61 Structural formula: Crystal form: white powder Salt form: free NMR value: 42 ) Reference Example 69 Structural formula: Crystal form: white powder Salt form: free NMR value: 43 ) (.Table 3 (continued)] Reference Example 70 Structural formula: Crystal form: white powder Salt form: free NMR value: 44 ) Reference Example 71 Structural formula: Crystal form: white powder Salt form: free NMR value: 45) LTable 3 (continued)] Reference Example 72 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol Melting point (°C): 142-144 Salt form: free Reference Example 73 Structural formula: Crystal form: white powder Salt form: free NMR value: 46 ) The NMR data 1) to 46) for the compounds prepared in Reference Examples 13 through 73 are as follows : 1) -N R (250 MHz, CdCl 3 ) δ ppm: 1.30-1.49 (2H, m), 1.66-1.91 (2H, m) , 2.36 (3H, s), 2.40-2.68 (3H, m), 2.80-3.04 (4H, m) , 3.04-3.21 (2H, m) , 7.06-7.15 (IH, m) , 7.15-7.23 (IH, m) , 7.54-7.66 (IH, m) , 8.50-8.59 (IH, m) . 2) J H-NMR (200 MHz, CDC1 3 ) δ pm: 1.25-1.55 (2H, m) , 1.55-1.94 (6H, m) , 2.26 (3H, s), 2.35-2.75 (5H, m) , 3.04-3.25 (2H, m), 7.06-7.39 (5H, m) . 3) J H-NMR (200 MHz, CDC1 3 ) δ ppm: 0.86-1.70 (4H, m), 1.04 (3H, d, J=6.2 Hz), 1.70-2.05 (2H, m), 2.41-2.85 (4H, ), 2.89-3.25 (2H, m) , 7.07-7.45 (5H, m) . 4) X H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.43 (2H, dq, J=4.0 Hz, 12.2 Hz), 1.70-1.90 (2H, m) , 2.34 (3H, s), 2.45-2.80 (7H, m), 3.08-3.25 (2H, m) , 3.79 (3H, s), 6.83 (2H, d, J=8.7 Hz), 7.11 (2H, d, J=8.7 Hz) 5) : H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.32-1.60 (2H, m) , : 1.60-1.89 (3H, ), 2.35 83H, s), 2.43-2.88 (7H, m), 3.02-3.28 (2H, m) , 3.86 (3H, s), 3.89 (3H, s), 6.69-6.89 (3H, m) . 6) -NMR (200 MHz, CDC1 3 ) δ ppm: 1.43 (2H, dq, J=4.0 Hz, 12.2 Hz), 1.70-1.88 (2H, m) , 2.35 (3H, s), 2.45-2.90 (7H, m), 3.07-3.25 (2H, m) , 3.80 (3H, s), 6.68-6.85 (3H, m), 7.13-7.38 (IH, m) . 7) X H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.41 (2H, dq, J=12 Hz, 4Hz), 1.65-2.03 (3H, m) , 2.30-2.95 (7H, m) , 2.37 (3H, s), 3.05-3.28 (2H, m) , 3.82 (3H, s), 6.75-7.00 (2H, m), 7.09-7.32 (2H, m) . 8) -NMR (200 MHz, CDC1 3 ) δ ppm: 1.25-1.57 (2H, ) , 1.57-2.00 (3H, m), 2.34 (3H, s), 2.40-2.67 (7H,m), 3.02- 3.24 (2H, m), 3.53 (IH, brs), 6.62 (2H, d, J=8.4 Hz), 6.98 (2H, d, J=8.4 Hz). 9) X H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.32-1.64 (2H, ) , 1.66-1.95 (2H, m) , 2.31 (3H, s), 2.34 (3H, s), 2.38-2.88 (7H, m), 3.07-3.38 (3H, m), 7.08 (4H, s). 10) ^-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.70-2.44 (4H, m) , 2.45-3.98 (9H, m), 2.81 (3H, d, J=4.6Hz ) , 6.75 (2H, d, J=8.4Hz), 7.14 (2H, d, J=8.4Hz), 8.39-9,78 (3H, m) , 9.79-10.28 (IH, m) . 11) X H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.20-1.53 (3H, m) , 1.66-1.85 (2H, m), 2.34 (3H, s), 2.40-2.76 (7H, m) , 2.46 (3H, s), 3.05-3.22 (2H, m) , 7.12 (2H, d, J=8.5 Hz), 7.20 (2H, d, J=8.5 Hz) . 12) X H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.55-1.95 (4H, m) , 2.28 (3H, s), 2.59-2.98 (7H, m) , 3.15-3.48 (2H, m) , 3.44 (IH, brs), 6.53-6.72 (3H, m) , 7.06 (IH, t, J=7.7 Hz), 9.33 (IH, brs) 13) X H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.28-1.55 (2H, ) , 1.55-2.05 (4H, m) , 2.10-2.80 (6H, m) , 2.87-3.48 (5H, m) , 7.12-7.40 (5H, m) . 14) : H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.63-2.40 (8H, m) , 2.70-3.02 (2H, m) , 3.02-3.65 (7H, m) , 6.09 (IH, brs), 7.25-7.48 (3H, m) , 7.53-7.65 (2H, ) , 9.33 (3H, brs). 15) ^-NMR (200 MHz, CDC1 3 ) δ ppm: 1.42-1.65 (2H, m) , 1.68-1.85 (2H, m), 1.92 (IH, brs), 2.28 (3H, s), 2.53- 2.85 (3H, m), 2.89 (2H, dd, J=9.5 Hz, 14.9 Hz), 3.04 (2H, dd, J=7.4 Hz, 14.9 Hz), 3.00-3.25 (2H, m), 3.49- 3.68 (IH, m), 7.06-7.24 (4H, ) . 16) -NMR (200 MHz, CDC1 3 ) δ ppm: 1.39 (3H, t, J=7.1 Hz), 3.52-3.70 (2H, m) , 3.86-4.06 (2H, m) , 4.36 82H, q, J=7.1 Hz), 5.62 (IH, brs), 7.61 (2H, d, J=8.9 Hz), 8.02 (2H, d, J=8.9 Hz) . 17) -NMR (200 MHz, CDC1 3 ) δ ppm: 3.95 (3H, s), 7.96 (IH, d, J=8.4 Hz), 8.05 (IH, dd, J=2.0 Hz, 8.4 Hz), 8.17 (IH, s), 8.28 (IH, d, J=2.0 Hz), 8.77 (IH, s) 18) : H-NMR (200 MHz, CDC1 3 ) δ ppm: 3.98 (3H, s), 7.61 (IH, dd, J=7.9 Hz, 8.1 Hz), 7.94 (IH, ddd, J=l .1 Hz, 2.3 Hz, 8.1 Hz), 8.08 (IH, ddd, J= 1.1 Hz, 1.8 Hz, 7.9 Hz), 8.14 (IH, s), 8.34 (IH, dd, J=l .8 Hz, 2.3 Hz), 8.66 (IH, s) 19) -NMR (200 MHz, CDC1 3 ) δ ppm: 1.16 (3H, t, J=7.1 Hz), 4.19 (2H, d, J=7.1 Hz), 7.45-7.73 (3H, m) , 8.01 (IH, dd, J=1.8 Hz, 7.6 Hz), 8.11 (IH, s), 8.34 (IH, s) 20) tø-NMR (200 MHz, DMSO-d 6 ) δ ppm: 3.40-3.60 (2H, m) , 3.76-4.04 (2H, m) , 7.20 (IH, brs), 7.66 (2H, d, J=9.0 Hz), 7.88 (2H, d, J=9.0 Hz), 12.60 (IH, brs). 21) : H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 8.02 (2H, d, J=6.8 Hz), 8.11 (2H, d, J=6.8 Hz), 8.30 (IH, s), 9.43 (IH, s), 13.18 (IH, brs). 22) tø-NMR (200 MHz, DMSO-d 6 ) δ ppm: 2.13 (3H, ε), 3.38 (2H, brs), 3.82 (3H, s), 5.23 (IH, brs), 7.23 (IH, d. J=1.4 Hz), 7.32 (IH, d, J=1.4 Hz). 23) X H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 2.29 (3H, s), 7.57 (IH, d, J=8.2 Hz), 7.92 (IH, dd, J=1.6 Hz, 8.2 Hz), 8.01 (IH, d, J=1.6 Hz), 8.27 (IH, s), 9.07 (IH, s), 13.19 (IH, brs). 24) ^-NMR (200 MHz, DMSO-d 6 ) δ ppm: 8.00-8.60 (3H, m) , 9.03 (IH, s), 9.52 (IH, s), 12.37-14.20 (IH, m) . 25) -NMR (200 MHz, DMSO-d 6 ) S ppm: 8.20-8.27 (2H, m), 8.29 (IH, s), 8.31-8.38 (IH, m), 9.25 (IH, s). 26) -NMR (200 MHz, DMSO-d 6 ) δ ppm: 6.9 (IH, brs), 7.78 (IH, d, J=8.5 Hz), 8.33 (IH, dd, J=1.7 Hz, 8.5 Hz), 8.39 (IH, s), 8.41 (IH, d, J=1.7 Hz), 9.25 (IH, s). 27) J H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 9.99 (2H, d, J=9.4 Hz), 10.00 (2H, d, J=9.4 Hz), 10.15 (IH, s), 14.07 (IH, brs), 14.86 (IH, brs). 28) : H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 7.70 (IH, dd, J=7.8 Hz, 8.0 Hz), 7.97 (IH, ddd, J=1.2 Hz, 1.8 Hz, 7.8 Hz), 8.14 (IH, ddd, J=1.2 Hz, 2.4 Hz, 8.0 Hz), 8.28 (IH, s), 8.39 (IH, dd, J=1.8 Hz, 2.4 Hz), 9.43 (IH, s), 13.38 (IH, brs). 29) ^-NMR (200 MHz, DMSO-d 6 ) δ ppm: 7.55-7.70 (3H, m) , 7.90 (IH, dd, J=2.0 Hz, 7.6 Hz), 8.17 (IH, s), 8.90 (IH, s), 13.12 (IH, brs). 30) ^-NMR (200 MHz, DMSO-d 6 ) δ ppm: 3.38 (IH, s), 7.89 (IH, dd, J=2.2 Hz, 8.5 Hz), 8.80 (IH, dd, J=0.6 Hz, 2.2 Hz), 8.32 (IH, s), 9.49 (IH, s). 31) ^- MR (200 MHz, DMSO-d 6 ) δ ppm: 3.98 (3H, s), 7.41 (IH, d, J=8.6 Hz), 8.02 (IH, dd, J=2.2 Hz, 8.6 Hz), 8.18 (IH, d, J=2.2 Hz), 8.23 (IH, s), 9.02 (IH, s), 13.04 (IH, brs). 32) tø-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.11 (3H, t, J=7.6 Hz), 2.13 (3H, s), 3.37 (2H, q, J=7.6 Hz), 2.44 (3H, s), 7.29 (IH, d, J=8.4 Hz), 7.54 (IH, d, J=8.4 Hz), 9.41 (IH, brs), 12.70 (IH, brs). 33) -NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.11 (3H, t, J=7.6 Hz), 2.21 (3H, s), 2.39 (2H, q, J=7.6 Hz), 2.45 (3H, s), 7.50 (IH, s), 7.70 (IH, s), 9.24 (IH, brs), 12.59 (IH, brs). 34) ^-NMR (200 MHz, CDC1 3 ) δ ppm: 1.32 (3H, t, J=7.6 Hz), 1.97 (3H, s), 2.26 (3H, s), 2.51 (2H, q, J=7.6 Hz), 3.63 (2H, s), 7.69 (IH, s), 7.82 (IH, s), 7.93 (IH, s), 11.00 (IH, brs) 35) ^-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.14 (3H, t, J=7.6 Hz), 2.23 (3H, s), 2.41 (2H, q, J=7.6 Hz), 2.92 (3H, s), 4.53 (2H, s), 7.80-7.92 (IH, ) , 7.92-8.05 (IH, m) , 9.45 (IH, brs), 13.00 (IH, brs). 36) ^-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.12 (3H, t, J=7.6 Hz), 2.18 (3H, s), 2.37 (2H, q, J=7.6 Hz), 5.35 (IH, d, J=11.0 Hz), 5.81 (IH, d, J=17.6 Hz), 6.80 (IH, dd, J=11.0 Hz, 17.6 Hz), 7.75 (IH, d, J=l .6 Hz), 8.00 (IH, d, J=1.6 Hz), 9.47 (IH, brs), 12.96 (IH, brs). 37) X H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.24 (3H, t, J=7.6 Hz), 2.36 (3H, s), 2.50 (2H, q, J=7.6 Hz), 8.14 (IH, d, J=1.7 Hz), 8.40 (IH, d, J=1.7 Hz), 9.15 (IH, brs). 38) : H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 0.92 (3H, t, J=7.5 Hz), 1.79 (2H, q, J=7.5 Hz), 2.20 (6H, s), 3.03 (3H, s), 7.77 (2H, s), 12.98 (IH, brs). 39) -NMR (200 MHz, DMSO-d 6 ) δ ppm: 2.66 (3H, ε), 7.80 (IH, s), 8.33 (IH, s). 40) : H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 2.04 83H, s), 6.50 (2H, brs), 7.65 (IH, d, J=1.9 Hz), 8.36 (IH, d, J=1.9 Hz) . 41) X H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.10 (3H, t, J=7.6 Hz), 2.39 (2H, q, J=7.6 Hz), 4.55 (2H, s), 4.50-6.00 (IH, m), 7.70-7.90 (2H, m) , 7.92-8.10 (IH, m) , 9.41 (IH, brs), 12.74 (IH, brs). 42) : H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.12 (3H, t, J=7.6 Hz), 2.18 (3H, s), 2.34 (2H, q, J=7.6 Hz), 4.42 (2H, s), 7.62-7.76 (IH, m) , 7.87-8.01 (IH, m) , 9.31 (IH, brs), 12.79 (IH, brs). 43) -NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.12 (3H, t, J=7.6 Hz), 2.32 (3H, s), 2.34 (2H, q, J=7.6 Hz), 3.82 (3H, s), 6.97 (IH, d, J=8.7 Hz), 7.81 (IH, d, J=8.7 Hz), 9.10 (IH, s), 12.57 (IH, s). 44) ^-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.15 (3H, t, J=7.6Hz), 2.36 83H, ε), 2.38 (2H, q, J=7.6 Hz), 7.47 (IH, d, J=8.4 Hz), 7.70 (IH, d, J=8.4 Hz), 9.60 (IH, ε), 13.13 (IH, brε). 45) -NMR (200 MHz, DMSO-d 6 ) 6 ppm: 1.11 (3H, t, J=7.6 Hz), 1.15 (3H, t, J=7.6 Hz), 2.32 (3H, s), 2.37 (2H, q, J=7.6 Hz), 2.48-2.70 (2H, m) , 7.18 (IH, d, J=8.2 Hz), 7.65 (IH, d, J=8.2 Hz), 9.34 (IH, s), 12.79 (IH, s). 46) X H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.09 (3H, t, J=7.5 Hz), 2.10 (3H, ε), 2.23 (3H, ε), 2.32 (2H, q, J=7.5 Hz), 7.04 (IH, d, J=8.0 Hz), 7.23 (IH, d, J=8.0 Hz), 9.28 (IH, brs). Reference Examples 74-80 By the method similar to that employed in Reference Example 3 or 4, and by using suitable starting materialε, there were prepared compoundε of Reference Exampleε 74-80 as shown in the following Table 4. Reference Examples 81-147 By the method similar to that employed in Reference Example 6 or 12, and by using suitable starting materials, there were prepared compounds of Reference Examples 81-147 as shown in the following Table 5. Reference Example 148 By the method similar to that employed in Reference Example 5, and by using suitable starting materials, there was prepared compound of Reference Example 148 as shown in the following Table 6. Reference Examples 149-156 By the method similar to that employed in Reference Example 3 or 4, and by using suitable starting materials, there were prepared compounds of Reference Examples 149-156 as shown in the following Table 7. Reference Examples 157-159 By the method similar to that employed in Reference Example 6 or 12, and by using suitable starting materials, there were prepared compounds of Reference Examples 157-159 as εhown in the following Table 8. Reference Exampleε 160-161 By the method similar to that employed in Reference Example 5, and by using suitable starting materials, there were prepared compounds of Reference Examples 160-161 as shown in the following Table 9. R Table 4 UN r / -N N R 2 (To be continued) Table 4 (Continued) Attached Shhet ( A ) for Table 4 Reference Example No. 1.H-NMR ( 200 MHz) ξ 74 (CDC1 3 ): 1.22-1.70 (3H, m), 1.7 2.13-2.72 (5H, m), 2.7 3.04-3.23 (2H, m), 3.8 76 (CDCl ): 77 (CDC1 3 ): 78 (CDC1 3 ): 79 (CDC1 3 ): (IH, m), 7.10-7.39 (5H, ) Table 5 Ra-OH (To be continued) (Continued) Table 5 Ra-OH (To be continued) Table 5 Ra-OH (Continued) (To be continued) (Continued) Table 5 Ra-OH (Continued) Table 5 Ra-OH (To be continued) (Continued) Table 5 Ra-OH (To be continued) (Continued) Table 5 Ra-OH (To be continued) Table 5 Ra-OH (Continued) (To be continued) (Continued) Table 5 Ra-OH (Continued) Table 5 Ra-OH (To be continued) Table 5 Ra-OH (Continued) (To be continued) (To be continued) (To be continued) Table 5 Ra-OH ( Continued) (To be continued) Table 5 Ra-OH (Continued) (To be continued) - (To be continued) Table 5 Ra-OH (Continued ) Attached Sheet (B) for Table 5 Reference , Example No. H-NMR (200 MHz) ό ppm 82 (DMSO-d,): 2.13 (3H, s), 6.34 ( 2H, brs), 7.73 ( IH, d, J=1.5 Hz) , 7.79 ( IH, d, J=1.5 Hz) 83 (250 MHz; DMSO-dg ) : 1.12 (3H, t, J=12.6 Hz), 2.32 (3H, s), 2.46 (2H, q, J=12.6 Hz), 7.93 (IH, s), 8.75 ( IH, s), 9.64 (IH, s), 2.60-4.33 (IH, brs) 86 (DMSO-d,.): 2.30 ( 3H, s), 7.32 (IH, s), 7.43 ( IH, o s), 10.82 (IH, s), 11.07 (IH, s), 12.27 (IH, brs) 87 (DMSO-d,): 1.11 (3H, t, J=7.6 Hz), 2.21 (3H, s), b 2.39 (2H, q, J=7.6 Hz), 2.39 (3H, s), 3.00-6.50 (IH, brs), 7.80 ( IH, s), 9.91 (IH, s) 90 (DMSO-db,): 5.35 (2H, s), 7.26-7.58 (5H, rn), 7.72 (IH, dd, J-1.5 Hz, 8.3 Hz), 7.78-7.95 (2H, ), 8.25 (IH, s), 9.04 (IH, s), 13.28 (IH, brs) 91 (DMSO-d 6 ): 3.88 (3H, s), 7.20 (IH, s), 7.23 (IH, s), 10.82 (IH, s), 11.12 (IH, s), 12.66 (IH, brs) 92 (DMSO-dg): 7.22 (IH, s), 7.49 (IH, s), 11.39 (IH, s), 11.42 (IH, s) 93 (DMSO-db,): 2.23 (3H,s), 3.54 (2H, s), 7.55-7.62 (IH, m), 7.62-7.68 (IH, ) , 10.73 (IH, s), 11.45-13.40 (IH, m) 94 (DMSO-d 6 ): 3.14 (3H, s), 3.61 (2H, s), 7.04 (IH, d, J=8.5 Hz), 7.79 (IH, d, J= 1.5 Hz), 7.90 (IH, dd, J=8.5 Hz, 1.5 Hz), 12.30-12.92 (IH, ) 95 (DMSO-d,): 1.35 (3H, d, J=7.5 Hz), 3.48 (IH, q, b J=7.5 Hz), 6.90 (IH, d, J=8.5 Hz), 7.75-7.90 (2H, m), 10.69 (IH, s), 12.38-12.83 (IH, ) Attached Sheet (B) for Table 5 Reference Example No. H-NMR ( 200 MHz ppm 96 (DMSO-d 6 2.24 (3H, s) 3.68 (2H, s), 7.11 ( IH, d, J=8.0 Hz) 7.41 (IH, d, J=8.0 Hz), 10.58 (IH, s , 12.70-13.00 (IH, m) 97 (DMSO-dg) 2.41 (3H, s) 3.47 (2H, s), 6.71 (IH, d, J=8.0 Hz) 7.78 ( IH, d, J=8.0 Hz) , 10.60 (IH, s , 12.15-12.60 (IH, m) 98 (DMSO-dg) 2.50 (3H, s) 3.46 (2H, s), 6.66 (IH, s) , 7.68 (IH s), 1-0.59 (IH, s), 12.10-12.60 IH, ) 99 (DMSO-d, ) 1.92 (3H, s) 4.69 (IH, s), 7.42 (2H, s), 11.11 (IH, s), 13.15-13.40 (IH, m] 100 (DMSO-dg) 3.51 (2H, s 6.89-7.08 (IH, ) 7.30-7.47 (IH, m), 7.57-7.70 (IH, m), 9.72 (IH, s) 11.35-14.25 (IH, m) 101 (DMSO-dg) 1.94 (3H, s) 4.75 (2H, s), 7.31 (IH, d, J=7.5 Hz) 7.47 (IH, d, J=7.5 Hz) , 11.10 (IH, s 13.10-13.54 (IH, m) 102 (DMSO-d, ) 3.67 (2H, s) 3.87 (3H, s), 7.02 (IH, d, J=9.0 Hz) 7.53 ( IH, d, J=9.0 Hz), 10.53 (IH, s 10.68 (IH, s) 103 (DMSO-dg) 3.75 (2H, s) 7.68 (IH, s), 7.84 (IH, d, J=2.0 Hz) 8.51 (IH, d, J=2.0 Hz) , 12.30-12.98 (IH, ) 104 (DMSO-d 6 1.26 (6H, s), 6.92 (IH, d, J=8.5 Hz), 7.79 (IH, d, J=1.5 Hz), 7.81 (IH, dd, J=8.5 Hz, 1.5 Hz), 10.68 (IH, s), 12.62 (IH, s) 105 (DMSO-d 6 ) 1.39 (6H, s), 3.87 (3H, s), 7.00 (IH, d, J=8.5 Hz), 7.58 (IH, d, J=8.5 Hz), 10.51 (IH, s), 12.50-12.90 (IH, ) 107 (250 MHz; DMSO-dg): 8.00 ( IH, s), 8.05 ( IH, d, J=8 Hz), 8.10 (IH, d, J=8 Hz), 8.18- 8.30 (2H, ), 8.48 (IH, dd, J=8.2 Hz, 2.0 Hz) , 13.39 (IH, brs) Attached Sheet (B) for Table 5 Reference , ~ Example No. H-NMR (200 MHz) ό ppm 108 (DMSO-d,): 1.26 (6H, s), 2.24 (3H, s), 7.63 (IH, b d, J=0.5 Hz), 7.66 ( IH, d, J=0.5 Hz), 10.72 (IH, s), 12.35-12.70 (IH, m) 109 (DMSO-d,): 3.68 (3H, s), 3.73 ( 3H, s), 3.79 (3H, 6 s), B.50-6.60 (IH, ), 6.62 ( IH, d, J=2.0 Hz), 7.05 (IH, d, J=8.0 Hz), 7.15-7.28 (IH, m), 7.46-7.62 (2H, m), 12.84-13.01 (IH, m) 114 (DMSO-d,): 6.39 (2H, d, J=8.1 Hz), 6.93 (IH, t, 6 J=8.1 Hz), 7.42 (2H, d, J=8.5 Hz), 7.89 (2H, d, J=8.5 Hz), 9.22 (2H, brs), 10.29-14.49 (IH, brs) 120 (DMSO-d^): 5.00 (2H, s), 5.16 (4H, s), 7.11 (2H, 6 s), 7.20-7.56 (17H, m) , 7.60 (IH, d, J=7.9 Hz), 7.69 (IH, s) 122 (DMSO-d,): 6.32 (IH, dd, J=8.5 Hz, 2.5 Hz), 6.43 b (IH, d, J=2.5 Hz), 7.12 (IH, d, J=8.5 Hz), 7.61 (2H, d, J=8.5 Hz), 7.90 (2H, d, J=8.5 Hz), 8.71-10.34 (2H, m), 11.47-13.68 (IH, ) 123 (CDC1-): 2.06 (3H, s), 2.08 (3H, s), 2.32 (3H, s), 7.05 (IH, d, J=2.0 Hz), 7.10 (IH, dd, J=8.5 Hz, 2.0 Hz), 7.32 (IH, d, J=8.5 Hz), 7.43 (IH, d, J=8.0 Hz), 7.91 (IH, d, J-1.5 Hz), 8.05 (IH, dd, J=8.0 Hz, 1.5 Hz), 9.20-10.20 (lH,m) 131 (DMSO-d,): 1.12 (3H, t, J=7.0 Hz), 3.17-3.40 (2H, b m), 7.84-8.10 (4H, m), 8.50-8.79 (IH, ), 13.05-13.31 (IH, m) 135 (DMSO-d,): 7.05-7.20 (IH, m), 7.28-7.46 (2H, ), 6 7.70-7.88 (2H, ), 7.98-8.15 (4H, m), 10.39 (IH, s), 13.11-13.35 (IH, ) 136 (DMSO-d,): 1.12 (3H, t, J=7.0 Hz), 3.14-3.43 (2H, b m), 7.58 (IH, t, J=8.0 Hz), 7.96-8.17 (2H, m), 8.41 ( IH, t, J=1.5 Hz), 8.56- 8.78 (IH, rn), 13.05-13.24 ( IH, m) Attached Sheet (B) for Table 5 Reference -, Example No. H-NMR (200 MHz) < ppm 137 (DMSO-d,): 1.13 (3H, t, J=7.0 Hz), 3.15-3.45 (2H, b m), 7.93 (IH, d, J=8.0 Hz), 8.10-8.30 (IH, ), 8.30-8.50 (IH, m), 8.70-8.98 (IH, m), 13.50-13.90. (IH, m) 138 (DMSO-d,): 1.05 " (3H, t, J=7.6 Hz), 2.33 ( 2H, q, b J=7.6 Hz), 6.32 (IH, d, J=3.6 Hz), 7.19 (IH, d, J=3.6 Hz), 11.37 (IH, s), 12.74 (IH, brs) 140 (DMSO-db,): 1.11 (3H, t, 3 = 1. 0 Hz), 3.12-3.38 ( 2H, m), 7.70 (IH, d, J=8.0 Hz), 8.26 (IH, dd, J=8.0 Hz, 1.5 Hz), 8.42 ( IH, d, J=1.5 Hz), 8.73 (IH, t, J=5.5 Hz), 13.22-14.22 (IH, ) 141 (DMSO-d,): 4.42 (2H, s), 7.75 (IH, d, 3=8 . 0 Hz), 8.03 (IH, d, J=8.0 Hz), 8.12 (IH, s), 8.78 (IH, s), 13.24 (IH, brs) 147 (DMSO-d 6 ): 6.26 (IH, dd, J=8.0 Hz, 2.0 Hz), 6.37 (IH, d, J=2.0 Hz), 6.96 (IH, d, J=8.0 Hz), 7.21 (IH, d, J=8.0 Hz), 7.36 (IH, dd, J=8.0 Hz, 1.5 Hz), 7.45 ( IH, d, J=1.5 Hz), 9.19 (IH, s), 9.29 ( IH, s), 9.40 (IH, s), 12.33-12.95 (IH, m) 23 Table 6 Ra-OR Table 7 (To be continued) Attached Sheet (C) for Table 7 Reference Example No. 1.H-NMR (200 MHz) ε0 ppm 151 (250 MHz; CDC1 3 ) : 1.31-1.56 (2H, m), 1.72-1.90 (2H, m), 2.16 (3H, s), 2.21 (3H, s), 2.37 (3H, s), 2.45-2.70 (3H, m), 2.85 152 (CDCl ): 153 (CDCl ): 154 (CDC1 3 ): 155 (CDCl ): Table 8 Ra-OH 0 C 23 Table 9 Ra-OR Example 1 42 ml of diethyl cyanophosphonate and 34 ml of triethylamine were dropwise added, in this order, to a solution of 49.2 g of 3,5-dimethyl-4-propionylamino- benzoic acid and 46.8 g of 4-[N-methyl-N-(2-phenyl- ethyl)amino]piperidine in 300 ml of DMF, at 5-10°C (the container inside temperature) with cooling in an ice- ethanol bath. The bath was removed and the mixture was stirred for 30 minutes. The mixture was then poured into 2 liters of ice water. The resulting mixture was extracted with ethyl acetate ( 500 ml x 2). The extract was washed with water ( 600 ml x 2) and a saturated aqueous sodium chloride solution in this order, and then concentrated under reduced pressure. To the residue was added 1 liter of ethanol for dissolution. To the solu¬ tion was added 20 ml of concentrated hydrochloric acid. The mixture was concentrated under reduced pressure. The concentration was stopped when the liquid volume became half of the original volume. The concentrate was ice-cooled. The resulting crystals were collected by filtration and recrystallized from water to obtain 81 g of 4-[N-methyl-N-(2-phenylethyl)amino]-1-(3,5-dimethyl- 4-propionylaminobenzoyl)piperidine hydrochloride as a white powder. Melting point: 260-263°C (decompd.) Using suitable starting materials, the compounds of Examples 2-257 described later were obtained in the same manner as in Example 1. Example 2 1.0 ml of phenyl isocyanate was added to a solution of 1.0 g of 4-[N-methyl-N-(2-phenylethyl)- amino]piperidine in 15 ml of chloroform. The mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added diethyl ether for crystallization. The resulting crystals were collected by filtration and recrystallized from ethyl acetate to obtain 0.7 g of 4-[N-methyl-N-(2-phenylethyl)amino]-l- anilinocarbonylpiperidine as colorless prism-like crystals. Melting point: 105-107°C Using suitable starting materials, the compounds of Examples 46 and 258-262 described later were obtained in the same manner as in Example 2. Example 3 A catalytic amount of p-toluenesulfonic acid was added to a solution of 0.45 g of 4-oxo-l-[4-(1,2,4- triazol-1-yl)benzoyl]piperidine and 0.39 g of 2-(4- chlorophenyl)ethylamine in 10 ml of toluene. The mixture was refluxed by heating, for 5 hours while removing the generated water using a Dean-Stark trap. The reaction mixture was concentrated under reduced pressure. To the residue was added 10 ml of ethanol. Thereto was added 70 mg of sodium borohydride at room temperature. The mixture was stirred at room tempera¬ ture overnight. The reaction mixture was made acidic with cocentrated hydrochloric acid and then concentrated under reduced pressure. To the residue was added ice water. The mixture was made basic with an aqueous sodium hydroxide solution and extracted with two 30-ml portions of ethyl acetate. The extract was washed with water and a saturated aqueous sodium chloride solution in this order, dried with sodium sulfate, and concen¬ trated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography (eluant: methylene chloride/methanol = 25/1) and then recrystallized from ethyl acetate to obtain 4-[2-(4-chlorophenyl)ethylamino]-l-[4-(l,2,4- triazol-l-yl)benzoyl]piperidine as a white powder. Melting point: 131-132.5°C By the method similar to that of employed in Example 3, and by using suitable materials, there were prepared compounds of Examples 1 and 2 as mentioned above, as well as compounds of Examples 4 - 90 and 92 - 262 as shown in following Table 10. CTable 10) Table 10 ( continued ) . Example 6 Structural formula: Crystal form: colorless scales Recrystallization solvent: ethanol Melting point (°C): 235-237 Salt form: hydrochloride Example 7 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol Melting point (°C): 158-160 Salt form: 1/2 fumarate { Table 10 ( continued ) ) Example 8 Structural formula: Crystal form: light yellow amorphous Salt form: hydrochloride NMR value: 47) Example 9 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol Melting point (°C): 218-220 (decompd.) Salt form: hydrochloride {Table 10 (continued)) {Table 10 (continued)) {Table 10 (continued)) { Table 10 ( continued ) ) Example 16 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol Melting point (°C): 138-140 Salt form: oxalate Example 17 Structural formula: 0 NHCCzHs Crystal form: white powder Recrystallization solvent: ethanol Melting point (°C): 244-246 Salt form: hydrochloride 4/22826 - 201 - { Table 10 ( continued ) ) Example 18 Structural formula: Crystal form: white amorphous Salt form: hydrochloride NMR value: 51 ) Example 19 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol Melting point (°C): 186-188 (decompd. ) Salt form: oxalate 4/22826 - 202 - { Table 10 ( continued ) ) Example 20 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol Melting point (°C): 234-237 (decompd. Salt form: hydrochloride Example 21 Structural formula: ,-Q Crystal form: white powder Recrystallization solvent: ethanol Melting point (°C): 238-240 (decompd. ) Salt form: hydrochloride 4/22826 - 203 - { Table 10 ( cont inued ) ) Example 22 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol Melting point (°C): 228-230 (decompd. Salt form: hydrochloride Example 23 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-water Melting point (°C): 234-236 Salt form: hydrochloride { Table 10 ( continued ) ) Example 24 Structural formula: N0 2 Crystal form: white powder Recrystallization solvent: ethanol-water Melting point (°C): 220-222 (decompd. ) Salt form: oxalate Example 25 Structural formula: Crystal form: colorless scales Recrystallization solvent: ethyl acetate Meltin gpoint (°C): 132-134 Salt form: free 4/22826 - 205 - { Table 10 ( continued ) ) Example 26 Structural formula: Crystal form: colorless prisms Recrystallization solvent: ethanol Melting point (°C): 236-238 Salt form: hydrochloride Example 27 Structural formula: Crystal form: white powder Recrystallization solvent: ethyl acetate Melting point (°C): 118-120 Salt form: free 4/22826 - 206 - {Table 10 (continued)) /22826 - 207 - {Table 10 (continued)) { Table 10 ( continued ) ) Example 32 Structural formula: Crystal form: white amorphous Salt form: dihydrochloride NMR value: 55) Example 33 Structural formula: Crystal form: white amorphous Salt form: dihydrochloride NMR value: 56) /22826 - 209 - {Table 10 (continued)) /22826 - 210 - { Table 10 ( continued ) ) Example 36 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol Melting point (°C): 225-227 Salt form: hydrochloride Example 37 Structural formula: IC / CU 3 \)7 <. - • C<rC»H .: J ~ \ Crystal form: white powder Recrystallization solvent: isopropanol Melting point (°C): 220-222 Salt form: hydrochloride {Table 10 (continued)) 4/22826 - 212 { Table 10 ( continued ) ) Example 40 Structural formula: Crystal form: white amorphous Salt form: hydrochloride NMR value: 57) Example 41 Structural formula: 2 - 2 > Crystal form: colorless prisms Recrystallization solvent: isopropanol Melting point (°C): 218-220 Salt form: hydrochloride {Table 10 (continued)) Crystal form: light yellow powder Recrystallization solvent: ethyl acetate-n-hexane Melting point . CO : 84-87 Salt form: free { Table 10 ( continued ) ) Example 44 Structural formula: C rystal form: colorless thick syrup Salt form: free NMR value: 159) Example 45 Structural formula: Crystal form: light yellow needles Recrystallization solvent: ethanol Melting point (°C): 200-202 Salt form: hydrochloride { Table 10 ( continued ) ) Example 46 Structural formula: Crystal form: colorless prisms Recrystallization solvent: ethanol Melting point (°C): 210-212 Salt form: hydrochloride Example 47 Structural formula: Crystal form: colorless prisms Recrystallization solvent: ethyl acetate-ethanol Melting point CO: 140-142 Salt form: hydrochloride /22826 - 216 - {Table 10 (continued)) { Table 10 ( continued ) ) Example 50 Structural formula: CH 3 Crystal form: white powder Recrystallization solvent: ethyl acetate-ethanol Melting point (°C): 187-189 Salt form: hydrochloride Example 51 Structural formula: Crystal form: white powder Recrystallization solvent: ethyl acetate-ethanol Melting point (°C): 203-205 Salt form: hydrochloride { Table 10 ( continued ) ) Example 52 Structural formula: Crystal form: white powder Recrystallization solvent: ethyl acetate-ethanol Melting point ( °C) : 139-141 Salt form: hydrochloride Example 53 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol Melting V point (°C): 224-227 (decompd, Salt fotm: hydrochloride {Table 10 (continued)) {Table 10 (continued)) 4/22826 - 221 - { Table 10 ( continued ) ) Example 58 Structural formula: Crystal form: colorless prisms Recrystallization solvent: ethanol-ethyl acetate Melting point (°C): 174-178 Salt form: hydrochloride Example 59 Structural formula: Crystal form: white powder Recrystallization solvent: ethyl acetate Melting point (°C): 175-176 Salt form: hydrochloride 4/22826 - 222 - {Table 10 (continued)) { Table 10 ( continued ) ) Example 62 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol Melting point (°C): 196-197 Salt form: oxalate Example 63 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-ethyl acetate Melting point (°C): 214-218 Salt form: hydrochloride /22826 - 224 - { Table 10 ( continued ) ) Example 64 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-ethyl acetate Melting point CO: 198.5-200 Salt form: oxalate Example 65 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-ethyl acetate Melting point ( °C) : 132-133 Salt form: oxalate /22826 - 225 - { Table 10 ( continued ) ) Example 66 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-ethyl acetate Melting point CC): 229-230.5 Salt form: hydrochloride Example 67 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-ethyl acetate Melting point CO: 232-232.5 Salt form: hydrochloride { Table 10 ( continued ) ) Example 68 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-ethyl acetate Melting point (°C): 222-223 Salt form: hydrochloride Example 69 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-ethyl acetate Melting point (°C): 203-204.5 Salt form: hydrochloride 4/22826 - 227 - { Table 10 ( continued ) ) Example 70 Structural formula: Crystal form: white powder Melting point (°C): 226-237 Salt form: dihydrochloride NMR value: 59) Example 71 Structural formula : Crystal form: white powder Recrystallization solvent: ethyl acetate-n-hexane Melting point (°C): 70-72 Salt form: free {Table 10 (continued)) { Table 10 ( continued ) ) Example 74 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-ethyl acetate Melting point (°C): 231.5-232.5 Salt form: hydrochloride Example 75 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-ethyl acetate Melting point (°C): 195-196 Salt form: hydrochloride { Table 10 ( continued ) ) Example 76 Structural formula: Crystal form: white powder Recrystallization solvent: ethyl acetate-n-hexane Melting point CO : 92-94 Salt form: free Example 77 Structural formula: Crystal form: colorless thick syrup Salt form: free NMR value: 63 ) 4/22826 - 231 - {Table 10 (continued)) {Table 10 (continued)) 4/22826 - 233 - {Table 10 (continued)) { Table 10 ( continued ) ) Example 84 Structural formula: Crystal form: white amorphous Salt form: dihydrochloride NMR value: 65 ) Example 85 Structural formula: R 1 CH 3 <■ ■ <(CH 2 ) ■■ O Crystal form: white amorphous Salt form: hydrochloride NMR value: 66 ) 4/22826 - 235 - { Table 10 ( continued ) ) Example 86 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-ethyl acetate Melting point (°C): 210-212 Salt form: hydrochloride Example 87 Structural formula: Crystal form: white powder Recrystallization solvent: ethyl acetate-diethyl ether Melting point (°C): 85-86 Salt form: free { Table 10 ( continued ) ) Example 88 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol Melting point (°C) : 164-168 Salt form: oxalate Example 89 Structural formula: Crystal form: white powder Recrystallization solvent: ethyl acetate-n-hexane Melting point ( °C) : 114.5-116 Salt form: free ' 4/22826 237 - { Table 10 ( continued ) ) Example 90 Structural formula: Crystal form: white amorphous Salt form: dihydrochloride NMR value: 67) Example 91 Structural formula: Crystal form: white powder Recrystallization solvent: ethyl acetate Melting point (°C): 131τl32.5 Salt form: free /22826 - 238 - { Table 10 ( continued ) ) Example 92 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol Melting point (°C): 223-225.5 Salt form: hydrochloride Example 93 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-water Melting point (°C): 279-281 (decompd.) Salt form: hydrochloride { Table 10 ( continued ) ) Example 94 Structural formula: CH 3 K * I -NHCHCH <r ■ Crystal form: white powder Recrystallization solvent: ethanol Melting point (°C): 224-227 Salt form: oxalate Example 95 Structural formula: Crystal form: white powder Recrystallization solvent: dichloromethane-ethyl acetate Melting point (°C): 137-138 Salt form: free { Table 10 ( continued ) ) Example 96 Structural formula: Crystal form: white powder Recrystallization solvent: dichloromethane-diethyl ether Melting oint (°C): 168-169 Salt form: free Example 97 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol Melting point (°C): 203-205 Salt form: hydrochloride /22826 - 241 - {Table 10 (continued)) {Table 10 (continued)) { Table 10 ( continued ) ) Example 102 Structural formula: Crystal form: white powder Recrystallization solvent: ethyl acetate-diethyl ether Melting point CO : 96-98 Salt form: free Example 103 Structural formula: Crystal form: white powder Recrystallization solvent: ethyl acetate-ethanol Melting point C : 181-182 Salt form: free { Table 10 ( continued ) ) Example 104 Structural formula: Crystal form: yellow powder Recrystallization solvent: ethyl acetate Melting point CO: 160.4-162.0 Salt form: free Example 105 Structural formula: Crystal form: light yellow powder Recrystallization solvent: ethyl acetate-diethyl ether Melting point CO : 88.5-89.0 Salt form: free { Table 10 ( continued ) ) Example 106 Structural formula: Crystal form: white amorphous Salt form: hydrochloride NMR value: 71) Example 107 Structural formula: Crystal form: white amorphous Salt form: trihydrochloride NMR value: 72) 4/22826 - 246 - {Table 10 (continued)) { Table 10 ( continued ) ) Example 110 Structural formula: Crystal form: white powder Recrystallization solvent: ethyl acetate Melting point (°C): 147-148 Salt form: free Example HI Structural formula: Hv Vϋ- Crystal form: white powder Recrystallization solvent: dichloromethane-diethyl ether Melting point CO: 133-134 Salt form: free {Table 10 (continued)) { Table 10 ( continued ) ) Example 114 Structural formula: Crystal form: light yellow powder Recrystallization solvent: ethyl acetate Melting point (°C): 150-151 Salt form: free Example 115 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-ethyl acetate Melting point CO : 155-160 Salt form: free {Table 10 (continued)) { Table 10 ( continued ) ) Example 118 Structural formula: Crystal form: white amorphous Salt form: free NMR value: 75 ) Example 119 Structural formula: Crystal form: white amorphous Salt form: hydrochloride NMR value: 76 ) . { Table 10 ( continued ) ) Example 120 Structural formula: Crystal form: white amorphous Salt form: dihydrochloride NMR value: 77 ) Example 121 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol Melting point (-°C): 194.5-195.5 Salt form: free { Table 10 ( continued ) ) Example 122 Structural formula: Crystal form: white amorphous Salt form: free NMR value: 78) Example 123 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-ethyl acetate Melting point CO: 214-216 Salt form: hydrochloride {Table 10 (continued)) {Table 10 (continued)) Example 126 Structural formula: Crystal form: white amorphous Salt form: free NMR value: 81) Example 127 Structural formula: Crystal form: white amorphous Salt form: hydrochloride NMR value: 82) { Table 10 ( continued ) ) Example 128 Structural formula : : Crystal form: white amorphous Salt form: free NMR value: 83 ) Example 129 Structural formula: Crystal form: white powder Recrystallization solvent: dichloromethane-diethyl ether Melting point (°C): 191-193 Salt form: free {Table 10 (continued)) /22826 - 258 - {Table 10 (continued)) { Table 10 ( continued ) ) Example 134 Structural formula: Crystal form: light yellow powder Recrystallization solvent: ethanol-ethyl acetate Melting point (°C): 180-181 Salt form: free Example 135 Structural formula: NHCONHCHj Crystal form: white amorphous Salt form: hydrochloride NMR value: 86 ) {Table 10 (continued)) 22826 - 261 - {Table 10 (continued)) {Table 10 (continued)) {Table 10 (continued)) { Table 10 ( continued ) ) Example 144 Structural formula: Crystal form: white powder Recrystallization solvent: dichloromethane-diethyl ether Melting point (°C): 140-142.5 Salt form: free Example 145 Structural formula: Crystal form: white powder Recrystallization solvent: dichloromethane-diethyl ether Melting point (°C): 133-134 Salt form: free { Table 10 ( continued ) ) Example 146 Structural formula: Crystal form: colorless needles Recrystallization solvent: dichloromethane-diethyl ether Melting point CO: 168-170 Salt form: free Example 147 Structural formula: Crystal form: light yellow amorphous Salt form: free NMR value: 94 ) { Table 10 ( continued ) ) Example 148 Structural formula: Crystal form: white amorphous Salt form: hydrochloride NMR value: 95) Example 149 Structural formula: Crystal form: white amorphous Salt form: free NMR value: 96 ) {Table 10 (continued)) {Table 10 (continued)) /22826 - 269 - {Table 10 (continued)) {Table 10 (continued)) {Table 10 (continued)) { Table 10 ( continued ) ) Example 160 Structural formula: Crystal form: white powder Recrystallization solvent: dichloromethane-diethyl ether Melting point CO : 105-107 Salt form: free Example 161 Structural formula: Crystal form: colorless prisms Recrystallization solvent: ethyl acetate Melting point . ( β C): 98-101 Salt form: free {Table 10 (continued)) {Table 10 (continued)) {Table 10 (continued)) { Table 10 ( cont inued ) ) Example 168 Structural formula: Crystal form: white amorphous Salt form: hydrochloride NMR value: 107) Example 169 Structural formula: Crystal form: white amorphous Salt form: hydrochloride NMR value: 108 ) { Table 10 ( continued ) ) Example 170 Structural formula: Crystal form: white amorphous Salt form: hydrochloride NMR value: 109 ) Example 171 Structural formula: Crystal form: white powder Recrystallization solvent: ethyl acetate-n-hexane Melting point (°C): 84.5-87 Salt form: free { Table 10 ( cont inued ) ) Example 172 Structural formula : 2 - Crystal form: white powder Recrystallization solvent: ethanol-ethyl acetate Melting point (°C): 162.5-163.5 Salt form: hydrochloride Example 173 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-diethyl ether Melting point CC): 211-214 Salt form: hydrochloride /22826 - 279 - {Table 10 (continued)) { Table 10 ( continued ) ) Example 176 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-water Melting point (°C): 198-200 Salt form: free Example 177 Structural formula: Crystal form: white powder Recrystallization solvent: methanol Melting point (°C): 209-210 Salt form: free {Table 10 (continued)) - 282 - {Table 10 (continued)) /22826 - 283 - { Table 10 ( continued ) ) Example 182 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-ethyl acetate Melting point (°C): 234-235.5 Salt form: hydrochloride Example 183 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-ethyl acetate Melting point CO: 247.5-248.5 Salt form: hydrochloride 2826 - 284 - {Table 10 (continued)) 22826 - 285 - {Table 10 (continued)) { Table 10 ( continued ) ) Example 188 Structural formula: Crystal form: white needles Recrystallization solvent: dichloromethane-n-hexane Melting point (°C): 109-111 Salt form: free Example 189 Structural formula: Crystal form: white powder Recrystallization solvent: methanol-water Melting point (°C): 258-260 Salt form: hydrochloride { Table 10 ( continued ) ) Example 190 Structural formula: Crystal form: light yellow amorphous Salt form: dihydrochloride NMR value: 118 ) Example 191 Structural formula: Crystal form: light yellow powder Recrystallization solvent: ethyl acetate-n-hexane Melting point CO: 126-128 Salt form: free {Table 10 (continued)) {Table 10 (continued)) { Table 10 ( continued ) ) Example 196 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-water Melting point (°C): 219-220 (decompd.) Salt form: hydrochloride Example 197 Structural formula: 2 ) 2 - Crystal form: white amorphous Salt form: hydrochloride NMR value: 122 ). 4/22826 - 291 - {Table 10 (continued)) {Table 10 (continued)) { Table 10 ( continued ) ) Example 202 Structural formula: Crystal form: white amorphous Salt form: dihydrochloride NMR value: 126) Example 203 Structural formula: Crystal form: colorless scales Recrystallization solvent: ethanol Melting point ( °C) : 115-116 Salt form: free { Table 10 ( continued ) ) Example 204 Structural formula: Crystal form: white powder Recrystallization solvent: ethyl acetate-ethanol Melting point (°C): 173-175 Salt form: hydrochloride Example 205 Structural formula: Crystal form: white amorphous Salt form: hydrochloride NMR value: 127 ) /22826 - 295 - { Table 10 ( continued ) ) Example 206 Structural formula: CH 3 C- Crystal form: white powder Recrystallization solvent: ethyl acetate-n-hexane Melting point (°C): 104-105 Salt form: free Example 207 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-water Melting point (°C): 243-246 (decompd.) Salt form: hydrochloride {Table 10 (continued)) 4/22826 - 297 - {Table 10 (continued)) /22826 _ 298 - { Table 10 ( continued ) ) Example 212 Structural formula: Crystal form: light yellow amorphous Salt form: hydrochloride NMR value: 131) Example 213 Structural formula: Crystal form: white powder Melting point CC): 243-245.5 (decompd. ) Salt form: hydrochloride { Table 10 ( continued ) ) Crystal form: white powder Recrystallization solvent: ethanol Melting point CO : 220-222 Salt form: hydrochloride Example 215 Structural formula: Crystal form: white powder Recrystallization solvent: ethyl acetate-ethanol Melting point (°C): 244-246 Salt form: hydrochloride { Table 10 ( continued ) ) Example 216 Structural formula : Crystal form: white powder Recrystallization solvent: ethyl acetate-ethanol Melting point (°C): 237-239 (decompd.) Salt form: hydrochloride Example 217 Structural formula: Crystal form: white powder Recrystallization solvent: ethyl acetate-ethanol Melting point (°C): 184.5-185 Salt form: hydrochloride {Table 10 (continued)) { Table 10 ( continued ) ) Example 220 Structural formula : CH: -N ,/ 1 <(CH 2 ) 2 -^ Crystal form: white powder Melting point CO : 201-204 Salt form: dihydrochloride Example 221 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-ethyl acetate Melting point (°C): 178-179 Salt form: oxalate /22826 - 303 - {Table 10 (continued)) 4/22826 - 304 - {Table 10 (continued)) {Table 10 (continued)) { Table 10 ( continued ) ) Example 228 Structural formula: Crystal form: light yellow amorphous Salt form: dihydrochloride NMR value: 140 ) Example 229 Structural formula: 0 II CH 3 C- Crystal form: white powder Recrystallization solvent: ethanol Melting point (°C): 257-260 (decompd.) Salt form: hydrochloride { Table 10 ( cont inued ) ) Example 230 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-ethyl acetate Melting point (°C): 206-209 Salt form: hydrochloride Example 231 Structural formula: Crystal form: white powder Recrystallization solvent: dichloromethane-diethyl ether Melting point (°C): 138-139 Salt form: free " { Table 10 ( continued ) ) Example 232 Structural formula: Crystal form: colorless prisms Recrystallization solvent: ethanol-ethyl acetate Melting point (°C): 110-112 Salt form: hydrochloride Example 233 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-ethyl acetate Melting point (°C): 136-137 Salt form: free " {Table 10 (continued)) { Table 10 ( continued ) ) Example 236 Structural formula : 0 H0CH 2 C- ,-Q Crystal form: colorless prisms Recrystallization solvent: ethanol-ethyl acetate Melting-point ( °C) : 177-178 Salt form: hydrochloride Example 237 Structural formula: Crystal form: white powder Recrystallization solvent: ethanol-ethyl acetate Melting point CC): 211-215 Salt form: hydrochloride {Table 10 (continued)) {Table 10 (continued)) {Table 10 (continued)) {Table 10 (continued)) {Table 10 (continued)) {Table 10 (continued)) {Table 10 (continued)) { Table 10 ( continued ) ) Example 252 Structural formula Crystal form: white powder Recrystallization solvent: ethanol Melting point (°C): 211-213 Salt form: hydrochloride Example 253 Structural formula: : Crystal form: white powder Recrystallization solvent: ethanol-n-hexane Melting point (°C): 206-207 Salt form: hydrochloride {Table 10 (continued)) {Table 10 (continued)) {Table 10 (continued)) CH s CW^ H C- Crystal form: colorless prisms Recrystallization solvent: ethanol Melting point (°C): 159-160 Salt form: free 22826 _ 322 - {Table 10 (continued)) /22826 - 323 - (-Table 10 ( cont inued ) ) Example 262 Structural formula: 0 II CHs-HNC- Crystal form: colorless prisms Recrystallization solvent: ethyl acetate-ethanol Melting point CO: 140-142 Salt form: hydrochloride 47) H-NMR (250 MHz, DMSO-d 6 ) δ ppm: 1.60-1.90 (2H, m), 1.90-2.40 82H, m) , 2.60-4.00 (11H, m), 4.40-4.90 (IH, ), 7.20-7.40 (5H, m) , 7.70 (2H, d, J=8.8 Hz), 7.85-7.95 (3H, ) , 8.83 (IH, s), 9.71 (IH, s), 11.10- 11.30 (IH, m) . 48) -NMR (250 MHz, DMSO-d 6 ) δ ppm: 1.60-1.85 (2H, m), 1.90-2.20 (2H, m), 2.78 (3H, d, J=4.7 Hz), 2.80-3.70 (7H, m), 4.00-4.50 (2H, m), 6.90-7.10 (3H, m), 7.20-7.40 (5H, m), 10.55-10.75 (IH, m) , 10.80 (IH, s), 10.83 (IH, s). 47) -NMR (250 MHz, DMSO-d 6 ) δ ppm: 1.50-1.80 (2H, m), 1.85-2.25 (2H, ) , 2.63 (3H, d, J=4.2 Hz), 2.79 (3H, d, J=4.8 Hz), 2.95-3.45 (6H, m) , 3.50-3.80 (2H, m) , 4.40-4.70 (IH, m), 6.21 (IH, q, J=4.8 Hz), 6.91 (IH, d, J=7.4 Hz), 7.20-7.40 (7H, m) , 7.54 (IH, s), 8.88 (IH, s), 10.45-10.55 (IH, m) . 48) -NMR (250 MHz, DMSO-d 6 ) δ ppm: 1.50-1.80 (2H, m), 1.90-2.20 (2H, m) , 2.79 (3H, d, J=4.8 Hz), 2.90-3.45 (6H, ), 3.50-3.90 (4H, ) , 4.40-4.80 (IH, ), 5.00-5.25 (2H, ), 5.75-5.95 (IH, ) , 6.40-6.50 (IH, m) , 6.92 (IH, d, J=7.2 Hz), 7.20-7.50 (7H, m) , 7.55 (IH, s), 8.90 (IH, s), 10.10-10.40 (IH, ) . 49) -NMR (250 MHz, DMSO-d 6 ) 8 ppm: 1.50-2.25 (8H, m), 2.30-2.50 (2H, m), 2.78 (3H, d, J=4.6 Hz), 3.00-3.40 (7H, m), 3.50-3.90 (3H, ) , 4.35-4.80 (IH, m) , 7.30-7.55 (9H, m), 10.60-10.90 (IH, m) . 50) -NMR (250 MHz, DMSO-d 6 ) δ ppm: 1.50-1.80 (2H, m), 1.90-2.20 (2H, ) , 2.79 (3H, d, J=4.8 Hz), 2.90-3.45 (6H, m), 3.50-3.90 (4H, m), 4.40-4.80 (IH, ) , 5.00-5.25 (2H, m), 5.75-5.95 (IH, M) , 6.40-6.50 (IH, m) , 6.92 (IH, d, J=7.2 Hz), 7.20-7.50 (7H, m) , 7.55 (IH, s), 8.90 (IH, s), 10.10-10.40 (IH, m) . 51) X H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.50-2.25 (8H, m), 2.30-2.50 (2H, m) , 2.78 (3H, d, J=4.6 Hz), 3.00-3.40 (7H, m), 3.50-3.90 (3H, m) , 4.35-4.80 (IH, m) , 7.30-7.55 (9H, m), 10.60-10.90 (IH, m) . 52) tø-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.22 (3H, t, J=7.5 Hz), 1.60-1.90 (2H, m) , 1.90-2.35 (2H, ) , 2.70- 2.85 (3H, ), 2.88 (2H, q, J=7.5 Hz), 3.00-3.80 (8H, m) , 4.40-4.90 (IH, ), 7.20-7.45 (5H, m) , 7.70 (4H, s), 7.80 (IH, d, J=2.1 Hz), 7.89 (IH, d, J=2.1 Hz), 11.05-11.35 (IH, ), 14.70-15.35 (IH, m) . 53) X H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.23 (3H, t, J=7.4 Hz), 1.55-1.95 (2H, ) , 1.95-2.40 (2H, m) , 2.34 (3H, ), 2.77 (3H, d, J=4.2 Hz), 2.84 (2H, q, J=7.4 Hz), 2.95-3.80 (8H, m) , 4.45-4.90 (IH, m) , 7.20-7.45 (5H, m) , 7.59 (IH, s), 7.68 (4H, s), 11.10-11.40 (IH, m) , 14.80- 15.20 (IH, m) . 54) tø-NMR (200 MHz, DMSO-d 6 ) 6 ppm: 1.45-1.90 (2H, m), 1.90-2.35 (2H, ) , 2.60-3.50 (9H, m) , 3.50-3.80 (2H, m), 4.40-4.85 (IH, m) , 7.18-7.45 (5H, m) , 7.68 (2H, d, J=8.4 Hz), 7.80 (2H, s), 8.31 (2H, d, J=8.4 Hz), 10.95- 11.40 (IH, m), 14-70-15.90 (2H, m) . 55) ^-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.57-1.93 (2H, m), 1.93-2.40 (2H, ), 2.78 (3H, d, J=4.8 Hz), 2.90-3.50 (6H, m), 3.50-4.00 (2H, m) , 4.30-5.00 (IH, m) , 7.20-7.43 (5H, m), 7.50-7.65 (3H, m) , 8.05-8.25 (4H, m) , 8.75 (IH, d, J=4.8 Hz), 11.00-11.40 (IH, ) . 56) tø-NMR (250 MHz, DMSO-d 6 ) δ ppm: 1.50-1.88 (2H, ), 1.96-2.24 (2H, m), 2.72 (3H, s), 2.76 (3H, d, J=4.8 Hz), 2.80-3.03 (2H, m) , 3.03-3.48 (4H, m), 3.48-3.70 (IH, m), 4.03-4.40 (2H, ) , 5.50-6.50 (IH, m) , 6.64 (2H, d, J=8.6 Hz), 7.18-7.45 (7H, m) , 10.85-11.20 (IH, m) . 57) : H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.50-1.90 (2H, ), 1.90-2.25 (2H, m), 2.64 (3H, d, J=4.0 Hz), 2.78 (3H, d, J=4.6 Hz), 2.55-3.70 (7H, m) , 3.86 (3H, s), 3.90-4.70 (2H, m), 6.80-7.05 (3H, m) , 7.20-7.40 (5H, ) , 8.10 (IH, s), 8.16 (IH, d, J=8.2 Hz). 58) -NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.50-1.84 (2H, m), 1.85-2.38 (2H, ) , 2.23 (3H, s), 2.66 (3H, d, J=3.1 Hz), 2.81 (3H, s), 2.90-3.51 (6H, m) , 3.51-4.02 (2H, m) , 4.30-4.87 (IH, m) , 6.61-6.80 (IH, m) , 6.92 (IH, d, J=7.6 Hz), 7.19 (IH, d, J=7.8 Hz), 7.24-7.49 (5H, m) , 7.94 (IH, s), 7.99 (IH, s), 10.59-10.85 (IH, m) . 59) -NMR (200 MHz, DMSO-d 6 ) 8 ppm: 1.55-1.93 (2H, m), 1.93-2.35 (2H, ) , 2.70-3.45 (6H, m) , 2.78 (3H, d, J=4.6 Hz), 3.45-3.85 (2H, ) , 4.35-4.85 (H, m) , 7.17- 7.50 (5H, m), 7.64 (2H, d, J=8.6 Hz), 7.83 (2H, d, J=8.6 Hz), 9.36 (2H, s), 10.85-11.20 (IH, m) . 60) tø-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.60-1.95 (2H, ), 1.95-2.38 (2H, m) , 2.82 (3H, s), 2.70-3.35 (2H, m) , 3.35-3.91 (6H, ) , 4.40-4.91 (IH, m) , 7.46-7.80 (4H, m) , 8.00 (2H, d, J=8.6 Hz), 8.07-8.22 (IH, m) , 8.30 (IH, s), 8.62-8.78 (IH, m) , 9.42 (IH, s), 11.02-11.40 (2H, m) . 61) ^-N R (200 MHz, DMSO-d 6 ) δ ppm: 1.60-1.93 (2H, ), 1.93-2.38 (2H, m) , 2.65-3.53 (6H, ) , 2.79 (3H, d, J=4.8 Hz), 3.53-3.85 (2H, m) , 3.93 (3H, s), 4.40-4.90 (IH, ), 7.10-7.45 (7H, m) , 7.72 (IH, d, J=8.0 Hz), 8.23 (IH, s), 9.01 (IH, s), 10.70-11.05 (IH, m) . 62) ^-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.55-1.90 (2H, m), 1.90-2.33 (2H, m) , 2.70-3.50 (6H, m), 2.80 (3H, d, J=4.8 Hz), 3.50-4.00 (2H, ), 4.35-4.90 (IH, ), 7.03 (IH, dd, J=1.6 Hz, 8.2 Hz), 7.16 (IH, d, J=l .6 Hz), 7.21-7.44 (5H, m) , 7.69 (IH, d, J=8.2 Hz), 8.22 (IH, s), 9.05 (IH, s), 10.30-10.65 (IH, m) , 11.07 (IH, s). 63) ^-NMR (200 MHz, CDD1 3 ) δ ppm: 1.10-2.10 (5H, m), 2.70-3.00 (4H, m) , 3.00-3.25 (3H, m) , 3.55-3.90 (IH, m), 4.35-4.75 (IH, m) , 7.10-7.40 (5H, m) , 7.53 (2H, d, J=8.7 Hz), 7.74 (2H, d, J=8.7 Hz), 8.12 (IH, s), 8.60 (IH, s). 64) -NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.60-2.38 (4H, m), 2.79 (3H, d, J=4.6 Hz), 2.70-3.02 (IH, m) , 3.02-3.88 (7H, ), 4.50-4.84 (IH, m) , 7.20-7.50 (5H, m) , 7.84 (IH, dd, J=1.6 Hz, 8.2 Hz), 8.03 (IH, d, J=1.6 Hz), 8.24 (IH, d, J=8.2 Hz), 8.32 (IH, s), 9.20 (IH, s), 11.01-11.39 (IH, m) . 65) H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.40-1.98 (2H, m), 1.98-2.35 (2H, m) , 2.55-2.75 (IH, m) , 2.75 (3H, d, J=4.8 Hz), 2.95-3.48 (5H, m) , 3.48-3.75 (IH, m) , 3.90- 4.18 (IH, m), 4.30-4.58 (IH, m) , 5.32 (2H, s), 7.18-7.44 (5H, m), 8.01 (IH, s), 8.51 (IH, s), 11.10-11.45 (IH, ) . 66) • 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.53-1.90 (2H, m), 1.90-2.30 (4H, m) , 2.60-4.20 (8H, m) , 3.71 (3H, d, J=4.6 Hz), 4.40-4.86 (IH, m), 7.15-7.45 (5H, m), 7.64 (2H, d, J=8.6 Hz), 7.98 (2H, d, J=8.6 Hz), 8.31 (IH, s), 9.42 (IH, s), 10.72-10.06 (IH, m) . 67) X H- MR (200 MHz, DMSO-d 6 ) δ ppm: 1.33-1.83 (2H, m), 1.85-2.25 (4H, m) , 2.35 (2H, t, J=7.0 Hz), 2.43-2.65 (IH, m), 2.72 (3H, d, J=4.6 Hz), 2.85-3.42 (5H, m) , 3.42-3.70 (IH, m) , 3.80-4.08 (IH, m), 4.26 (2H, t, J=6.8 Hz), 4.40-4.65 (IH, ) , 7.15-7.45 (5H, m) , 8.32 (IH, s), 8.85-9.50 (IH, m) , 9.02 (IH, s), 11.20-11.55 (IH, m) . 68) 1 H-N R " (200 MHz, DMSO-d 6 ) δ ppm: 1.60-1.93 (2H, m), 1.93-2.35 (2H, m) , 2.70-3.55 (6H, m) , 2.78 (3H, d, J=4.8 Hz), 3.55-3.95 (2H, m) , 4.45-4.90 (IH, ) , 7.17- 7.43 (5H, ), 7.46 (IH, d, J=7.6 Hz), 7.65 (IH, t, J=7.6 Hz), 7.88-8.05 (2H, m) , 8.27 (IH, s), 9.38 (IH, s), 10.85-11.25 (IH, m) . 69) -NMR (200 MHz, DMSO-d 6 ) 8 ppm: 1.25-2.30 (4H, m), 2.55-2.95 (4H, m) , 2.95-4.15 (7H, m) , 4.40-4.70 (IH, m), 7.18-7.45 (5H, m) , 7.45-7.83 (4H, m) , 8.20 (IH, s), 8.90-9.03 (IH, ), 10.95-11.30 (IH, m) . 70) -NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.51-1.88 (2H, m), 1.88-2.38 (2H, m) , 2.76 (3H, d, J=4.8 Hz), 2.93-3.49 (6H, m), 3.49-3.83 (2H, m) , 4.28-4.80 (IH, ) , 5.49 (2H, s), 7.17-7.51 (5H, m) , 8.04 (IH, s), 8.75 (IH, s), 10.90-11.20 (IH, m) . 71) -NMR (200 MHz, DMSO-d 6 ) 8 ppm: 1.73-2.05 (2H, m), 2.05-2.45 (2H, ) , 2.68-3.95 (6H, m), 4.14-4.36 (IH, m), 4.40-4.89 (2H, m) , 7.38-7.54 (3H, m) , 7.54-7.80 (4H, m), 7.96 (2H, d, J=8.6 Hz), 8.29 (IH, s), 8.0 (IH, s), 10.55-10.85 (IH, m) . 72) tø-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.60-1.91 * ( 2H, m), 1.91-2.40 (2H, m), 2.79 (3H, d, J=4.2 Hz), 2.65-3.90 (8H, m), 4.30-4.89 (IH, ) , 7.62 (2H, d, J=8.6 Hxz ) , 7.82-8.10 (3H, m) , 8.29 (IH, s), 8.51 (IH, d, J=8.2 Hz), 8.83-8.90 (IH, m), 8.90-9.01 (IH, m) , 9.40 (IH, s), 11.25-11.58 (IH, m) . 73) X H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.60-1.91 (2H, m), 2.04-2.39 (2H, m) , 2.74 (3H, s), 2.80-3.96 (10H, ), 4.17-5.10 (2H, m), 7.63 (2H, d, J=8.6 Hz), 7.73 (IH, d, J=8.0 Hz), 7.79 (IH, d, J=8.0 Hz), 7.95 (2H, d, J=8.6 Hz), 8.29 (IH, s), 8.33 (IH, t, J=8.0 Hz), 8.40 (IH, s), 11.25-11.55 (IH, m) . 74) : H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.31 (3H, t, J=7.1 Hz), 1.34-1.70 (2H, m), 1.70-2.07 (2H, m), 2.37 (3H, s), 2.60-3.20 (7H, m) , 3.65-4.00 (IH, m) , 4.20 (2H, q, J=7.1 Hz), 4.55-4.93 (IH, m) , 6.63 (IH, brs), 6.88- 6.91 (IH, ), 7.10-7.26 (2H, m) , 7.35 (IH, brs), 7.58 (2H, d, J=8.6 Hz), 7.73 (2H, d, J=8.6 Hz), 8.13 (IH, s), 8.60 (IH, s). 75) X H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.37-1.67 (2H, ), 1.67-2.00 (2H, m) , 2.35 (3H, s), 2.50-3.17 (7H, m) , 2.71 (3H, d, J=4.7 Hz), 3.60-3.97 (IH, m), 4.50-4.90 (IH, m), 5.44 (IH, q, J=4.7 Hz), 7.04 (2H, d, J=8.5 Hz), 7.22 (2H, d, J=8.5 Hz), 7.38 (IH, s), 7.52-7.56 (2H, m) , 7.73-7.77 (2H, m) , 8.12 (IH, s), 8.62 (IH, s). 76) ^-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.68-1.96 (2H, m), 1.96-2.35 (2H, m) , 2.65-4.08 (6H, m) , 2.83 (3H, d, J=4.6 Hz), 3.73 (3H, s), 4.21-4.99 (2H, m) , 6.82-7.06 (4H, m), 7.65 (2H, d, J=8.7 Hz), 7.98 (2H, d, J=8.7 Hz), 8.31 (IH, s), 9.42 (IH, s), 10.81-11.05 (IH, m) . 77) ^- MR (200 MHz, CDC1 3 ) 8 ppm: 1.6-2.0 (2H, m) , 2.3-2.7 (2H, m), 2.83-3.2 (2H, m) , 2.85 (3H, d, J=5 Hz), 3.5-3.7 (4H, m), 4.0-5.0 (3H, ) , 6.88 (2H, d, J=7.8 Hz), 7.03 (IH, t, J=7.2 Hz), 7.26-7.36 (2H, m) , 7.58 (2H, d, J=8.6 Hz), 7.78 (2H, d, J=8.6 Hz), 8.14 (IH, s), 8.65 (IH, s), 13.0-13.4 (IH, m) . 78) ^- MR (200 MHz, DMSO-d 6 ) δ ppm: 1.3-1.8 (4H, m), 2.26 (3H, s), 2.5-37 (8H, ) , 4.4-4.5 (IH, m) , 7.33 (2H, d, J=8.2 Hz), 7.56 (2H, d, J=8.6 Hz), 7.83 (2H, d, J=8.2 Hz), 7.91 (2H, d, J=8.6 Hz), 8.26 (IH, s), 9.34 (IH, s). 79) ^-NMR (200 MHz, CDC1 3 ) δ ppm: 1.35-2.10 (4H, m), 2.40-3.30 (7H, m) , 2.75 (2H, t, J=5.0 Hz), 3.30-4.10 (2H, ), 3.54 (2H, t, J=5.0 Hz), 4.81 (IH, brs), 7.07- 7.40 (5H, m), 7.55 (2H, dd, J=6.8 Hz, 2.0 Hz), 7.75 (2H, dd, J=6.8 Hz, 2.0 Hz), 8.12 (IH, s), 8.63 (IH, s). 80) ^-N R (200 MHz, CDC1 3 ) δ ppm: 1.33-1.67 (2H, m), 1.67-2.03 (2H, m) , 2.35 (3H, s), 2.57-3.20 (7H, m) , 2.80 (3H, d, J=4.7 Hz), 3.60-4.00 (IH, m) , 4.55-4.90 (IH, ), 4.97 (IH, q, J=4.7 Hz), 6.68 (IH, brs), 6.84 (IH, d, J=7.4 Hz), 7.03-7.06 (IH, m) , 7.15-7.26 (2H, m) , 7.53 (2H, d, J=8.6 Hz), 7.73 (2H, d, J=8.6 Hz), 8.13 (IH, s), 8.60 (IH, s). 81) 'H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.33-1.67 (2H, m), 1.67-2.00 (2H, m) , 2.15 (3H, s), 2.35 (H, s), 2.55- 3.20 (7H, m), 3.60-3.97 (IH, m) , 4.57-4.90 (IH, m) , 6.91-6.94 (IH, m) , 7.16-7.28 (2H, m) , 7.47-7.60 (IH, m), 7.53 (2H, d, J=8.3 Hz), 7.73 (2H, d, J=8.3 Hz), 8.02 (IH, brs), 8.12 (IH, s), 8.62 (IH, s). 82) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.2-1.7 (4H, m), 2.77 (3H, s), 2.6-3.2 (6H, m) , 3.5-3.7 (2H, m), 4.5- 4.8 (IH, ), 6.65-6.82 (2H, m), 7.0-7.1 (2H, m), 7.61 (2H, d, J=8.6 Hz), 7.94 (2H, d, J=8.6 Hz), 7.5-8.5 (2H, m), 8.26 (IH, s), 9.37 (IH, s). 83) -NMR (200 MHz, CDC1 3 ) δ ppm: 1.2-2.0 (4H, m) , 2.13 (3H, s), 2.47 (3H, s), 2.6-3.3 (7H, m) , 3.7-4.0 (IH, ), 4.6-4.9 (IH, m) , 6.98-7.22 (3H, m) , 7.53 (2H, d, J=8.6 Hz), 7.74 (2H, d, J=8.6 Hz), 7.90 (IH, d, J=8 Hz), 8.13 (IH, s), 8.59 (IH, s), 11.0 (IH, s). 84) ^- MR (200 MHz, DMSO-d 6 ) δ ppm: 1.60-2.00 (2H, m), 2.00-2.30 (2H, m) , 2.78 (3H, d, J=4.7 Hz), 2.87-3.70 (7H, ), 3.72-4.75 (2H, m) , 5.47 (2H, brs), 6.90 (IH, d, J=6.8 Hz), 7.23-7.45 (5H, ), 7.52 (IH, d, J=2.6 Hz), 7.60 (IH, dd, J=2.6 Hz, 6.8 Hz), 8.17 (IH, s), 9.11 (IH, s), 10.9-11.30 (IH, m). 85) ^-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.45-2.37 (4H, m), 2.38-4.30 (8H, m) , 2.81 (3H, d, J=4.6 Hz), 4.31-4.87 (IH, m), 6.78 (IH, t, J=7.2 Hz), 6.89 (IH, d, J=7.2 Hz), 7.09 (IH, d, J=7.2 Hz), 7.18 (IH, d, J=7.2 Hz), 7.65 (2H, d, J=8.4 Hz), 7.98 (2H, d, J=8.4 Hz), 8.31 (IH, s), 9.42 (IH, s), 9.75 (IH, brs), 10.72-11.11 (IH, ) . 86) -NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.50-2.36 (4H, m), 2.61 (3H, s), 2.80 (3H, d, J=3.8 Hz), 2.70-4.07 (7H, ), 4.15-5.26 (2H, m) , 6.60-7.92 (8H, m), 8.15 (IH, s), 8.22 (IH, s), 8.37 (IH, s), 9.00 (IH, s), 10.67-11.10 (IH, m). 87) : H-NMR (200 MHz, DMSO-d 6 ) 8 ppm: 1.6-1.9 (2H, ), 2.0 (3H, s), 2.15 (6H, s), 1.9-2.3 (2H, m) , 2.76 (3H, d, J=4.4 Hz), 2.8-4.0 (8H, m) , 4.4-4.8 (IH, m) , 7.1 (2H, s), 7.2-7.5 (5H, m) , 9.34 (IH, s), 10.8-11.0 (IH, m). 88) tø-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.5-1.8 (2H, m), 1.8-2.2 (2H, ), 2.15 (6H, s), 2.74 (3H, s), 2.5-3.8 (8H, m), 4.3-4.7 (IH, m), 5.74 (IH, d, J=10 Hz), 6.21 (IH, d, J=17 Hz), 6.52 (IH, dd, J=17 Hz, 10 Hz), 7.12 (2H, s), 7.2-7.4 (5H, m), 7.6 (IH, s), 10.8-11.1 (IH, m) . 89) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.4-2.4 (4H, ), 2.2 (6H, s), 2.77 (3H, d, J=4 Hz), 2.5-4.0 (8H, m) , 4.5-4.7 (IH, ), 7.17 (2H, s), 7.31 (5H, s), 7.52-7.56 (3H, m), 8.0 (2H, d, J=6.6 Hz), 9.88 (IH, s), 108-11.1 (IH, m) . 90) X H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.33-1.67 (2H, m), 1.67-2.00 (2H, m) , 2.16 (3H, s), 2.36 (3H, s), 2.57- 3.20 (7H, ), 3.60-3.93 (IH, m) , 4.53-4.93 (IH, m) , 7.11 (2H, d, J=8.4 Hz), 7.33 (IH, brs), 7.39 (2H, d, J=8.4 Hz), 7.53-7.57 (2H, m) , 7.72-7.77 (2H, ) , 8.12 (IH, s), 8.60 (IH, s). 91) X H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.5-2.4 (4H, m), 2.63 (3H, d, J=4.5 Hz), 2.81 (3H, d, J=4.5 Hz), 2.81-3.5 (6H, m), 3.5-3.8 (2H, m) , 4.5-4.8 (IH, ) , 6.6- 6.9 (IH, m), 6.90-7.05 (IH, m) , 7.14-7.23 (2H, m) , 7.61 (2H, d, J=8.6 Hz), 7.7-7.8 (IH, m) , 7.94 (2H, d, J=8;6 Hz), 8.19 (IH, s), 8.27 (IH, s), 9.37 (IH, s), 10.2-10.4 (IH, ) . 92) 'H-NMR (200 MHz, DMSO-d 6 ) 8 ppm: 1.6-2.32 (4H, m), 2.32 (6H, s), 2.76 (3H, d, J=4.6 Hz), 2.7-4.7 (9H, m), 7.19 (2H, s), 7.24-7.31 (5H, m) , 7.86 (IH, dd, J=8 Hz, 4 Hz), 8.3-9.0 (IH, m) , 8.70 (IH, d, J=8 Hz), 8.92 (IH, d, J=4 Hz), 9.36 (IH, s), 10.5 (IH, s), 11.00-11.30 (IH, m) . 93) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 0.94 (3H, t, J=7.2 Hz), 1.5-2.3 (6H, m) , 2.15 (6H, s), 2.2-2.4 (2H, m), 2.75 (3H, d, J=3.8 Hz), 2.5-4.8 (9H, m) , 7.09 (2H, s), 7.2-7.4 (5H, m), 9.35 (IH, s), 10.9-11.2 (IH, m) . 94) Η-NMR (200 MHz, CDC1 3 ) 8 ppm: 1.50-1.81 (2H, m), 1.81-2.15 (2H, m) , 2.65-3.28 (7H, m) , 3.63-4.15 (IH, m), 3.74 (2H, s), 3.77 (3H, s), 4.40-5.00 (IH, m) , 6.63- 6.75 (2H, m), 6.94 (IH, d, J=8.4 Hz), 7.58 (2H, d, J=8.7 Hz), 7.76 (2H, d, J=8.7 Hz), 8.13 (IH, s), 8.61 (IH, s). 95) Η-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.60-2.37 (4H, m), 2.05 (3H, s), 2.63-3.90 (8H, m), 2.88 (3H, d, J=4.0 Hz), 4.50-4.72 (IH, ) , 7.15-7.45 (5H, m) , 7.68 (IH, d, J=8.7 Hz), 8.26 (IH, s), 7.91 (IH, dd, J=2.6 Hz, 8.7 Hz), 8.26 (IH, s), 9.32 (IH, s), 9.88 (IH, brs), 10.60- 11.35 (IH, m) . 96) Η-NMR (200 MHz, CDC1 3 ) δ ppm: 1.60-1.69 (2H, m), 1.69-2.10 (2H, m) , 2.35 (3H, s), 2.55-3.74 (7H, m) , 2.72 (3H, d, J=4.6 Hz), 3.50-4.10 (IH, m) , 4.20-.90 (IH, ), 5.45-5.55 (IH, m) , 7.15-7.45 (5H, m) , 7.50-7.65 (2H, m), 8.08 (2H, s), 8.22 (IH, d, J=8.9 Hz), 8.50 (IH, s). 97) Η-NMR (200 MHz, DMSO-d 6 ) 8 ppm: 1.51-2.38 (4H, m), 2.82 (3H, d, J=4.6 Hz), 2.89 (6H, d, J=4.6 Hz), 2.62-4.92 (13H, m) , 6.85-7.17 (2H, m) , 7.19-7.45 (2H, m), 7.65 (2H, d, J=8.5 Hz), 7.98 (2H, d, J=8.5 Hz), 8.30 (IH, s), 9.41 (9.41 (IH, s), 10.42-10.83 (IH, m) , 11.01- 11.40 (IH, m) . 98) 'H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.42-2.25 (4H, m), 2.38-5.10 (13H, ), 2.81 (3H, s), 4.57 (2H, s), 6.70-7.04 (2H, m) , 7.05-7.38 (2H, m) , 7.53 (2H, s, J=8.6 Hz), 7.75 (2H, d, J=8.6 Hz), 8.11 (IH, s), 8.64 (IH, s), 10.43 (IH, brs). 99) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.55-1.93 (2H, ), 1.93-2.30 (2H, m), 2.76 (3H, d, J=4.6 Hz), 2.80-3.50 (6H, m), 3.50-3.75 (2H, m) , 3.75-4.80 (IH, m) , 3.94 (3H, s), 7.18-7.45 (6H, m) , 7.54 (IH, dd, J=2.2 Hz, 8.4 Hz), 7.72 (IH, d, J=2.2 Hz), 8.22 (IH, s), 9.00 (IH, s), 11.00-11.33 (IH, m) . 100) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.60-2.00 (2H, ), 2.00-2.43 (2H, m) , 2.26 (3H, s), 2.70-3.33 (2H, m) , 2.26 (3H, s), 3.40-3.97 (6H, m) , 4.00-5.60 (2H, m) , 7.44-7.56 (3H, m) , 7.72-7.78 (IH, m) , 7.85 (IH, d, J=7.9 Hz), 8.27-8.34 (IH, m) , 8.29 (IH, s), 8.75-8.77 (IH, m) , 8.96 (IH, s), 11.45 (IH, brs). 101) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.50-1.93 (2H, m), 1.93-2.25 (2H, m) , 2.70-3.50 (6H, m) , 2.77 (3H, d, J=4.6 Hz), 3.50-3.80 (IH, m) , 3.80-4.60 (2H, m) , 7.19 (IH, d, d=8.6 Hz), 7.20-7.45 (6H, m) , 7.70 (IH, d, J=2.0 Hz), 8.21 (IH, s), 9.02 (IH, s), 10.65-10.93 (IH, m) , 11.23 (IH, s). 102) Η-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.60-1.90 (2H, m), 1.97-2.40 (2H, m) , 2.82 (3H, s), 2.65-3.30 (2H, m) , 3.40-3.80 (5H, m), 4.30-5.70 (3H, m) , 7.35-7.60 (5H, m) , 7.76-7.82 (IH, ) , 7.89-7.93 (IH, m), 8.32-8.40 (IH, m) , 8.76-8.79 (IH, ) , 11.43 (IH, brs). 103) Η-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.55-1.90 (2H, m), 2.10-2.30 (2H, m) , 2.82 (3H, s), 2.65-3.20 (2H, m) , 3.50-4.50 (8H, m) , 3.80 (3H, s), 3.81 (3H, s), 7.01 (3H, s), 7.76-7.83 (IH, m) , 7.90-7.94 (IH, m), 8.33-8.40 (IH, m), 8.77-8.79 (IH, m) , 11.47 (IH, brs). 104) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1,6-1.9 (2H, m), 1.9-2.4 (4H, m) , 2.71-2.78 (10H, m), 3.0-3.5 (8H, m), 3.5-3.8 (IH, m) , 4.2-4.3 (2H, m) , 4.5-4.7 (IH, m) , 7.16-7.33 (7H, m) , 7.33 (IH, d, J=6.6 Hz), 8.23 (IH, s), 9.03 (IH, s), 10.5-10.7 (IH, m) , 10.9-11.1 (IH, m) . 105) Η-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.63-1.93 (2H, m), 1.97-2.33 (2H, m) , 2.83 (3H, s), 2.60-3.35 (3H, m) , 3.40-3.83 (4H, m) , 4.00-5.10 (3H, m) , 7.64 (2H, d, J=8.6 Hz), 7.68-7.77 (2H, ) , 7.83 (2H, d, J=8.6 Hz), 8.26 (IH, t, J=7.7 Hz), 8.75 (IH, d, J=4.6 Hz), 9.34 (2H, s), 11.37 (IH, brs). 106) Η-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.30-1.90 (2H, m), 1.90-2.29 (2H, m) , 2.02 (3H, s), 2.45-2.64 (IH, m) , 2.75 (3H, brs), 2.94-3.45 (5H, m), 3.45-3.68 (IH, m) , 3.85-4.05 (IH, m) , 4.47-4.65 (IH, ) , 7.35 (2H, d, J=8.5Hz), 7.43 (2H, d, J=8.5 Hz), 10.38 (2H, brs), 11.00-11.39 (IH, ) . 107) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.50-1.90 (2H, m), 1.90-2.25 (2H, ), 2.75 (3H, s), 2.85-3.48 (6H, m) , 3.48-3.70 (IH, m) , 3.79 (3H, s), 3.80 (3H, s), 3.80-4.85 (2H, m), 5.89 (2H, brs), 6.63 (2H, d, J=8.3 Hz), 6.91- 7.15 (5H, m), 10.20-11.70 (IH, m) . 108) Η-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.20-2.25 (4H, ), 2.55-2.90 (4H, m) , 2.90-3.80 (7H, m) , 4.40-4.65 (IH, m), 4.60 (2H, s), 4.80-6.00 (IH, m) , 7.16-7.45 (5H, m) , 7.45-7.75 (3H, m) , 8.17 (IH, s), 8.85-9.00 (IH, m) , 10.60-10.93 (IH, m) . 109) Η-NMR (200 MHz, DMSO-d 6 ) 8 ppm: 1.11 (3H, t, J=7.6 Hz), 2.33 (2H, q, J=7.6 Hz), 1.4-2.2 (4H, m) , 1.96 (1.7H, s), 2.05 (1.3H, s), 2.14 (3H, s), 2.5-2.8 (4H, m), 2.8-3.7 (7H, ) , 4.6-4.7 (IH, m) , 6.8-7.4 (7H, m), 9.27 (IH, s), 10.4-10.6 (IH, m) . 110) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.65-1.95 (2H, m), 1.95-2.30 (2H, m) , 2.84 (3H, s), 3.05-4.85 (10H, m) , 7.66 (IH, t, J=5.3 Hz), 7.73 (IH, d, J=7.6 Hz), 7.97- 8.10 (2H, m), 8.17-8.30 (2H, m) , 8.41 (IH, s), 8.71 (IH, d, J=5.3 Hz), 9.26 (IH, s), 11.07 (IH, brs). 111) Η-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.55-1.91 (2H, m), 1.91-2.33 (2H, ) , 2.22 (3H, s), 2.75 (3H, d, J=4.5 Hz), 2.82-3.91 (8H, ) , 4.40-4.80 (IH, s), 6.58-6.78 (3H, ), 7.10 (IH, dd, J=8.1 Hz, 8.1 Hz), 7.45-7.59 (3H, m), 8.25 (IH, s), 8.91 (IH, s), 8.98-10.10 (IH, m) , 10.98 (IH, brs). 112) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.50-1.90 (2H, m), 1.90-2.33 (2H, m) , 2.65-3.50 (6H, m) , 2.77 (3H, s), 3.50-4.05 (2H, ) , 4.35-4.85 (IH, m) , 5.37 (2H, brs), 6.68 (IH, dd, J=1.7 Hz, 7.9 Hz), 6.89 (IH, d, J=l .7 Hz), 7.16 (IH, d, J=7.9 Hz), 7.20-7.45 (6H, m) , 7.51 (IH, s), 8.30 (IH, s), 10.60-11.40 (IH, m) . 113) Η-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.52-1.91 (2H, m), 1.96-2.30 (2H, m) , 2.78 (3H, d, J=4.8 Hz), 2.80-3.75 (7H, ), 3.99-5.12 (4H, m) , 6.94 (IH, d, J=8.2 Hz), 7.20-7.51 (7H, m) , 8.30 (IH, s), 8.94 (IH, s), 10.92- 11.20 (IH, m) . 114) Η-NMR (200 MHz, DMSO-d 6 ) 8 ppm: 1.68-1.90 (2H, m), 1.90-2.21 (2H, m) , 2.01 (3H, s), 2.79 (3H, d, J=4.8 Hz), 2.90-4.25 (8H, m) , 4.25-4.89 (IH, ), 7.15-7.46 (5H, m), 7.56 (IH, dd, J=1.7 Hz, 8.2 Hz), 7.61 (IH, d, J=1.7 Hz), 7.93 (IH, d, J=8.2 Hz), 8.29 (IH, s), 8.97 (IH, s), 9.77 (IH, s), 10.92-11.18 (IH, m) . 115) Η-NMR (200 MHz, DMSO-d 6 ) 6 ppm: 1.14 (3H, t, J=7.6 Hz), 1.62-1.90 (2H, m) , 1.95 (3H, s), 2.00-2.30 (2H, m), 2.12 (3H, s), 2.37 82H, q, J=7.6 Hz), 2.79 (3H, d, J=6.6 Hz), 2.91-3.50 (7H, m) , 3.50-3.79 (IH, m) , 3.66 (2H, s), 4.41-4.81 (IH, m), 7.15-7.48 (7H, m) , 9.41 (IH, s), 10.95-11.19 (IH, m) . 116) Η-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.62-1.99 (2H, m), 1.99-2.41 (2H, m) , 2.79 (3H, d, J=4.6 Hz), 2.71-3.02 (IH, m), 3.02-3.51 (5H, M), 3.51-3.96 (2H, m) , 4.51-4.85 (IH, m), 7.20-7.48 (5H, m) , 7.82 (IH, dd, J=l .8 Hz, 8.0 Hz), 7.90 (IH, d, J=1.8 Hz), 7.92 (IH, d, J=8.0 Hz), 8.13 (IH, s), 8.14 (IH, s), 8.68 (IH, s),8.72 (IH, s), 11.10-11.34 (IH, ). 117) Η-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.10 (3H, t, J=7.6 Hz), 1.37-2.29 (10H, m) , 2.35 (2H, q, J=7.6 Hz), 2.59-2.91 (4H, m) , 2.91-3.74 (7H, m) , 4.58-4.83 (IH, m), 6.83-7.45 (7H, m) , 9.41 (IH, s), 10.70-11.00 (IH, m) . 118) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.15 (3H, t, J=7.6 Hz), 1.58-1.90 (2H, m) , 1.90-2.26 (2H, ) , 2.17 (6H, s), 2.36 (2H, q, J=7.6 Hz), 2.80 (3H, s), 3.20-4.00 (8H, m), 4.25-4.90 (IH, ), 7.12 (2H, s), 7.35-7.46 (IH, m), 7.48 (IH, d, J=7.7 Hz), 7.90 (IH, ddd, J=1.7, 7.7 Hz, 7.7 Hz), 8.58 (IH, d, J=4.0 Hz), 9.35 (IH, s), 10.70-11.15 (IH, m) . 119) Η-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.12 (3H, t, J=7.6 Hz), 1.19-1.49 (2H, ) , 1.49-1.90 (2H, m) , 2.06 (3H, s), 2.26 (3H, s), 2.35 (2H, wq, J=7.6 Hz), 2.59- 3.51 (7H, m), 3.51-4.00 (IH, m) , 4.10-4.65 (IH, m) , 4.90 (2H, brs), 6.40 (IH, d, J=2.0 Hz), 6.55 (IH, d, J=2.0 Hz), 7.10-7.40 (5H, ) , 8.32 (IH, s), 8.87 (IH, brs). 120) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 0.90 (3H, t, J=7.1 Hz), 1.58-1.72 (2H, m) , 1.78 (2H, q, J=7.1 Hz), 1.97-2.26 (2H, ) , 2.15 (6H, s), 2.77 (3H, d, J=4.0 Hz), 3.00 (3H, s), 3.01-3.47 (6H, m) , 3.47-3.95 (2H, m) , 4.30-4.87 (IH, m) , 7.08-7.55 (7H, m) , 10.75-11.12 (IH, m) . 121) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.08 (3H, t, J=7.6 Hz), 1.57-1.90 (2H, m) , 1.95-2.27 (2H, m) , 2.42 (2H, q, J=7.6 Hz), 2.75 (3H, d, J=3.4 Hz), 2.82-3.45 (6H, m), 3.45-4.00 (2H, m) , 4.31-4.87 (IH, m) , 7.17-7.49 (6H, m), 7.54 (IH, d, J=l.8 Hz), 7.82 (IH, d, J=8.2 Hz), 9.56 (IH, s), 11.12-11.42 (IH, m) . 122) Η-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.08 (3H, t, J=7.5 Hz), 1.40-1.81 (2H, m) , 1.81-2.30 (2H, m), 2.34 (2H, q, J=7.5 Hz), 2.60-2.88 (4H, ) , 2.88-3.70 (7H, m) , 3.75 (3H, s), 4.52-4.77 (IH, m) , 7.00-7.44 (7H, m),7.49 (IH, s), 10.15 (IH, s), 10.85-11.19 (IH, m) . 123) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.06 (3H, t, J=7.5 Hz), 1.55-1.90 (2H, m) , 1.90-2.32 (2H,m), 2.42 (2H, q, J=7.5 Hz), 2.77 (3H, d, J=4.4 Hz), 2.70-3.75 (8H, m), 3.86 (3H, s), 4.30-4.80 (IH, m) , 6.96 (IH, dd, J=1.6 Hz, 8.2 Hz), 7.06 (IH, d, J=1.6 Hz), 7.16-7.45 (5H, m), 8.06 (IH, d, J=8.2 Hz), 9.18 (IH, s), 10.81- 11.10 (IH, m). 124) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.08 (3H, t, J=7.5 Hz), 1.48-1.87 (2H, ) , 1.87-2.32 (2H, m) , 2.36 (2H, q, J=7.5 Hz), 2.66-2.92 (IH, m) , 2.76 (3H, d, J=4.6 Hz), 2.92-3.79 (7H, m) , 4.50-4.80 (IH, m) ,7.14-7.50 (7H, m), 7.70 (IH, d, J=13.2 Hz), 10.39 (IH, s), 10.70-10.98 (IH, m). 125) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.12 (3H, t, J=7.6 Hz), 1.50-1.90 (2H, ) , 1.90-2.30 (2H, m) , 2.19 (3H, s), 2.40 (2H, q, J=7.6 Hz), 2.70-2.86 (3H, m) , 2.89 (3H, s), 2.95-3.95 (8H, m) , 4.45-4.78 (IH, m) , 4.47 (2H, s), 7.18-7.45 (7H, m) , 9.44 (IH, s), 10.50-10.75 (IH, m). 126) 'H-NMR (200 MHz, DMSO-d 6 ) 8 ppm: 1.58-1.95 (2H, ), 1.95-2.26 (2H, ), 2.75 (3H, d, J=4.3 Hz), 2.80-3.84 (9H, m), 3.84-4.59 (2H, m), 6.99 (IH, d, J=9.1 Hz), 7.17-7.40 (5H, m) , 7.99 (IH, dd, J=2.0 Hz, J=9.1 Hz), 8.10 (IH, d, J=2.0 Hz), 8.22-8.46 (IH, m) , 10.96-11.20 (IH, m). 127) Η-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.55-1.93 (2H, ), 1.93-2.35 (2H, m) , 2.66 (3H, brs), 2.79 (3H, s, J=4.0 Hz), 2.90-3.50 (6H, m) , 3.50-4.10 (2H, ) , 4.30- 5.00 (IH, m), 7.15-7.45 (6H, ) , 7.55-8.10 (IH, m) , 10.55-11.00 (IH, m), 15.65-16.45 (IH, m) . 128) 'H-NMR (200 MHz, DMSO-d 6 ) 8 ppm: 1.52-1.88 (2H, m), 1.95-2.33 (2H, m) , 2.76 (3H, d, J=3.8 Hz), 2.84-3.48 (6H, M), 3.48-3.70 (IH, m) , 3.82-4.55 (2H, m) , 7.07 (IH, d, J=8.8 Hz), 7.19-7.42 (5H,m), 7.47 (IH, dd, J=8.8 Hz, 2.0 Hz), 7.76 (2H, s), 8.05 (IH, d, J=2.0 Hz), 11.07- 11.26 (IH, m) . 129) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.06 (3H, t, J=7.4 Hz), 1.59-1.91 (2H, m) , 1.91-2.26 (2H, m) , 2.38 (2H, q, J=7.4 Hz), 2.76 (3H, d, J=4.2 Hz), 2.85-3.50 (6H, m), 3.50-3.93 (2H, m) , 4.32-4.82 (IH, m), 7.20-7.45 (5H, m), 7.66-7.79 (2H, m) , 7.97 (IH, s), 10.51 (IH, s), 10.83-11.07 (IH, m) . 130) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.52-1.89 (2H, m), 1.97-2.28 (2H, m) , 2.76 (3H, s), 2.81-3.49 (7H, ) , 3.49-3.72 (IH, ) , 3.92-4.55 (3H, m) , 6.93 (IH, d, J=8.4 Hz), 7.05 (IH, d, J=8.4 Hz), 7.26-7.43 (6H, m) , 10.89- 11.19 (IH, m) . 131) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.42 (3H, t, J=7.6 Hz), 1.57-1.92 (2H, m), 1.92-2.30 (2H, m) , 2.76 (3H, d, J=4.0 Hz), 2.82-3.44 (8H, m) , 3.44-4.06 (2H, m) , 4.38-4.89 (IH, m) , 7.20-7.41 (5H, m) , 7.53 (IH, d, J=8.4 Hz), 7.75-7.89 (2H, m) , 11.01-11.43 (IH, m) . 132) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.09 (3H, t, J=7.3 Hz), 1.28-2.22 (7H, m) , 2.31 (2H, q, J=7.3 Hz), 2.56-3.64 (11H, m) , 3.77 (3H, s), 4.18-6.79 (3H, m), 6.92 (IH, d, J=8.5 Hz), 7.00-7.46 (6H, m) , 9.10 (IH, s). 133) 'H-NMR (200 MHz, DMSO-d 6 ) 8 ppm: 1.52-1.92 (2H, m), 1.98-2.27 (2H, m) , 2.18 (3H, s), 2.74 (3H, d, J=4.2 Hz), 2.81-3.52 (6H, m) , 3.52-3.73 (IH, m) , 3.85-4.63 (2H, m), 7.18-7.45 (5H, m) , 7.81 (IH, s), 8.04 (IH, s), 8.25 (2H, brs), 11.23-11.45 (IH, m) . 134) Η-NMR (200 MHz, DMSO-d 6 ) δ ppm: 3.05 (6H, t, J=7.4 Hz), 1.53-1.86 (2H, m) , 1.86-2.27 (2H, ) , 2.38 (2H, q, J=7.4 Hz), 2.40 (2H, q, J=7.4 Hz), 2.77 (3H, s), 2.56-3.48 (6H, ) , 3.49-3.72 (IH, m) , 3.72-4.16 (IH, m) , 4.20-4.82 (IH, ) , 7.13-7.47 (6H, m) , 7.64 (IH, s), 7.67 (IH, d, J=8.4 Hz), 9.67 (2H, s), 10.63 (IH, brs). 135) 'H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.22-1.62 (2H, m), 1.70-1.93 (4H, m) , 2.08 (2H, brs), 2.28-2.50 (2H, m), 2.34 (3H, ms ) , 2.50-2.84 (8H, m) , 2.90-3.09 (IH, m) , 3.83-4.00 (IH, m), 4.57-4.72 (IH, m) , 7.12-7.36 (5H, m) . 136) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.33-1.92 (2H, m), 1.92-2.32 (2H, m), 2.55-2.80 (IH, m) , 2.72 (3H, s), 2.85-3.49 (5H, m) , 3.49-3.70 (IH, ) , 3.70-4.02 (3H, m) , 4.37-4.60 (IH, ) , 7.13-7.47 (5H, ) , 8.01-8.69 (3H, m) , 11.50 (IH, brs). 137) Η-NMR (200 MHz, CDC1 3 ) δ ppm: 1.23-1.56 ( 2H, m), 1.62-1.91 (5H, m), 2.29-2.51 (2H, m), 2.34 (3H, s), 2.44 (3H, s), 2.51-2.86 (8H, m) , 2.90-3.09 (IH, m) , 3.84-4.00 (IH, m), 4.59-4.74 (IH, ) , 7.14-7.36 (5H, m) . 138) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.39-1.91 (2H, ), 2.01-2.38 (2H, m), 2.60-2.95 (IH, m), 2.72 (3H, s), 2.80 (6H, s), 2.95-3.50 (5H, m) , 3.50-3.85 (2H, m) , 4.22-4.60 (3H, m) , 7.18-7.46 (5H, m) , 9.84 (IH, brs), 11.57 (IH, brs). 139) 'H-NMR (200 MHz, DMSO-d 6 ) 8 ppm: 1.40-1.93 (2H, m), 2.03-2.32 (2H, m) , 2.35-2.95 (IH, m), 2.52 (3H, s), 2.72 (3H, s), 2.95-3.48 (5H, m) , 3.48-3.70 (IH, m) , 3.70-3.88 (IH, m) , 3.88-4.22 (2H, ) , 4.41-4.60 (IH, m) , 7.18-7.48 (5H, m) , 8.83-9.20 (2H, m), 11.41 (IH, brs). 140) Η-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.35-2.26 (6H, m), 2.26-2.63 (4H, m) , 2.69 (6H, s), 2.71 (3H, s), 2.89- 3.68 (7H, m), 3.92-4.12 (IH, m) , 4.44-4.62 (IH, m) , 7.15-7.43 (5H, m) , 10.73 (IH, brs), 11.25 (IH, brs). 141) Η-NMR (200 MHz, CDC1 3 ) δ ppm: 1.30-2.00 (8H, m), 2.20-2.50 (5H, m) , 2.55-3.20 (7H, m), 3.40-3.65 (2H, m), 3.65-4.00 (IH, ) , 4.60-4.90 (IH, m) , 7.04 (IH, d, J=7.6 Hz), 7.10-7.50 (7H, m) , 7.68 (IH, d, J=7.9 Hz), 8.36 (IH, brs). 142) 'H-NMR (200 MHz, CDC1 3 ) 8 ppm: 0.55-0.80 (0.4H, m), 1.15-1.93 (3.6H, ) , 1.42 (3H, t, J=7.1Hz), 2.23 (1,8H, s), 2.33 (1.2H, s), 2.45-2.80 (6.4H, m) , 2.80- 3.00 (0.6H, m), 3.23-3.43 (IH, m) , 4.42 (2H, q, J=7.1 Hz), 4.52-4.82 (IH, m) , 7.10-7.38 (5H, m) , 7.70 (IH, d, J=8.4 Hz), 7.95 (0.6H, s), 8.05-8.16 (1.4H, m) , 8.21 (IH, dd, J=1.8 Hz, 8.4 Hz), 8.50 (0.4H, s), 8.61 (0.6H, s). 143) Η-NMR (200 MHz, DMSO-d 6 ) 8 ppm: 1.50-1.80 (2H, m), 1.90-2.20 (2H, m), 2.79 (3H, d, J=4.4 Hz), 2.85-3.70 (9H, m), 3.80-4.70 (2H, m), 6.85 (IH, d, J=8.6 Hz),7.20- 7.45 (7H, m), 10.30-10.50 (IH, ) , 10.58 (IH, s). 144) 'H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.30-1.67 (2H, ), 1.67-2.05 (2H, m) , 2.38 (3H, s), 2.60-3.15 (7H, ) , 3.55-4.10 (3H, m) , 4.55-4.90 (IH, m) , 6.53-6.70 (3H, m) , 7.07-7.40 (6H, m) . 145) Η-NMR (200 MHz, DMSO-d 6 ) 8 ppm: 1.35-1.65 (2H, m), 1.70-1.95 (2H, m), 2.37 (3H, s), 2.55-3.00 (7H, m) , 3.85 (3H, s), 3.99 (2H, brs), 4.15-4.65 (2H, ), 6.64 (IH, d, J=7.9 Hz), 6.88 (IH, dd, J=l .7 Hz, 7.9 Hz), 6.92 (IH, d, J=1.7 Hz), 7.12-7.37 (5H, m) . 146) 'H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.20-1.64 (2H, ), 1.64-2.00 (2H, m) , 2.15 (3H, s), 2.35 (3H, s), 2.51- 3.15 (7H, m), 3.62-4.13 (IH, m) , 3.70 (2H, brs), 4.45- 4.92 (IH, m), 6.60-6.76 (2H, ) , 7.02 (IH, d, J=7.8 Hz), 7.10-7.38 (5H, m) . 147) 'H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.35-1.65 (2H, m), 1.65-1.95 (2H, m) , 2.16 (3H, s), 2.36 (3H, s), 2.53- 3.00 (7H, m), 3.79 (2H, brs), 4.05-4.65 (2H, m) , 6.62 (IH, d, J=8.1 Hz), 7.02-7.38 (7H, m) . 148) 'H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.24 (3H, t, J=7.5 Hz), 1.30-1.99 (4H, m) , 2.36 (3H, s), 2.51 (2H, q, J=7.5 Hz), 2.55-3.20 (7H, m) , 3.71 (2H, brs), 3.65-4.18 (IH, ), 4.45-4.98 (IH, m), 6.57-6.83 (2H, ) , 7.05 (IH, d, J=7.5 Hz), 7.11-7.40 (5H, m) . 149) Η-NMR (200 MHz, CDC1 3 ) δ ppm: 0.99 (3H, t, J=7.3 Hz), 1.22-1.97 (6H, m), 2.36 (3H, s), 2.46 (2H, t, J=7.6 Hz), 2.54-3.13 (7H, m) , 3.70 (2H, brs), 3.71-4.10 (IH, ), 4.50-4.90 (IH, m), 6.60-6.78 (2H, m) , 7.02 (2H, d, J=8.0 Hz), 7.11-7.37 (5H, m) , 150) 'H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.20-2.09 (4H, m), 2.37 (3H, s), 2.59-3.22 (7H, ) , 3.28-3.60 (IH, m), 4.59-4.94 (IH, m) , 7.09-7.48 (5H, m) , 7.55 (IH, d, J=8.3 Hz), 8.07 (IH, dd, J=2.1 Hz, 8.3 Hz), 8.17 (IH, s), 8.54 (IH, d, J=2.1 Hz), 8.71 (IH, s). 151) 'H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.23-2.15 (4H, m), 2.40 (3H, s), 2.50-3.21 (8H, ), 3.82 (3H, s), 4.55- 4.94 (IH, m), 6.82-6.96 (2H, m) , 7.04-7.30 (2H, m), 7.55 (2H, d, J=8.5 Hz), 7.75 (2H, d, J=8.5 Hz), 8.12 (IH, s), 8.62 (IH, s). 152) 'H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.25-2.10 (4H, m), 2.37 (3H, s), 2.55-3.30 (7H, ) , 3.58-3.99 (IH, m) , 3.80 (3H, s), 4.30-4.95 (IH, m) , 6.65-6.88 (3H, m) , 7.15-7.35 (IH, m) , 7.56 (2H, d, J=8.5 Hz), 7.75 (2H, d, J=8.5 Hz), 8.12 (IH, s), 8.60 (IH, s). 153) 'H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.2-2.0 (4H, m) , 2.36 (3H, s), 2.5-3.2 (7H, m), 3.6-3.8 (IH, m) , 4.5-4.8 (IH, m), 7.32-7.53 (3H, m) , 7.55 (2H, d, J=8.6 Hz), 7.74 (2H, d, J=8.6 Hz), 7.88 (IH, d, J=5 Hz), 8.13 (IH, s), 8.6 (IH, s). 154) Η-NMR (200 MHz, CDC1 3 ) δ ppm: 1.4-2.0 (4H, m) , 2.04 (1.6H, s), 2.06 (1.4H, s), 2.17 (3H, s), 2.35 (H, s), 2.5-3.0 (7H, m) , 3.5-3.8 (3H, m) , 4.7-4.8 (IH, m) , 6.4-6.57 (IH, m), 6.93-6.95 (IH, ), 7.16-7.32 (5H, m) . 155) Η-NMR (200 MHz, CDC1 3 ) δ ppm: 0.90-1.60 (3H, m), 1.65-2.10 (2H, m) , 2.47 (3H, s), 2.65-3.20 (7H, m) , 3.45-4.00 (IH, m), 4.30-4.85 (IH, m), 7.13 (2H, d, J=8.5 Hz), 7.21 (2H, d, J-=8.5 Hz ) , 7.33-7.46 (5H, ) . 156) 'H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.35-1.70 (2H, m), 1.70-2.10 (2H, ) , 2.38 (3H, s), 2.60-3.30 (7H, m) , 3.55-3.90 (IH, m) , 4.50-4.85 (IH, m) , 7.08 (IH, dd, J=1.0 Hz, 1.4 Hz), 7.14-7.38 (6H, m) , 7.51 (IH, d, J=8.1 Hz), 7.65 (IH, dd, J=l .0 Hz, 1.3 Hz), 7.75 (IH, dd, J=1.8 Hz, 8.1 Hz), 8.02 (IH, d, J=1.8 Hz). 157) 'H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.20-2.06 (4H, m), 2.21 (3H, s), 2.35 (3H, s), 2.50-3.11 (7H, m) , 3.48- 3.95 (3H, m), 4.65-4.91 (IH, m) , 6.41-6.58 (2H, m) , 6.85-7.05 (IH, m) , 7.10-7.40 (5H, m) . 158) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.50-1.80 (2H, m), 1.90-2.20 (2H, m) , 2.76 (3H, d, J=4.2 Hz), 2.65-2.95 (2H, m), 3.00-3.65 (5H, m), 4.20-4.45 (2H, m) , 7.20-7.40 (5H, ), 7.51 (IH, t, J=8.1 Hz), 7.78 (IH, d, J=8.1 Hz), 7.93 (IH, d, J=8.1 Hz), 8.50 (IH, s), 9.21 (IH, s), 10.65-10.95 (IH, m) . 159) 'H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.25-2.10 (4H, m), 2.36 (3H, s), 2.53-3.17 (7H, m) , 3.52-3.38 (IH, m) , 4.00-4.19 (2H, m), 4.36-4.54 (2H, m) , 4.57-4.90 (IH, ) , 7.15-7.36 (5H, m) , 7.43 (2H, dd, J=6.7 Hz, 1.8 Hz), 7.98 (2H, dd, J=6.7 Hz, 1.8 Hz ) . 160) 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.50-1.80 • ( 2H, ), 1.95-2.20 (2H, m), 2.08 (3H, s), 2.65-3.70 (7H, ), 2.75 (3H, s), 2.77 (3H, d, J=4.6 Hz), 4.10-4.40 (2H, m) , 5.51 (IH, brs), 6.46 (IH, d, J=8.4 Hz), 7.08 (IH, d, J=1.8 Hz), 7.16 (IH, dd, J=8.4 Hz, 1.8 Hz), 7.22-7.45 (5H, m), 10.42-10.70 (IH, m) . 161) Η-NMR (200 MHz, CDC1 3 ) δ ppm: 1.30-1.70 (2H, m), 1.70-2.05 (2H, m) , 2.39 (3H, s), 2.60-3.20 (8H, m) , 3.65-4.20 (IH, ) , 4.50-5.05 (IH, m) , 6.82 (2H, d, J=8.6 Hz), 7.13-7.60 (11H, ) . Example 263 0.78 g of potassium carbonate and 1.14 g of 2- (3-pyridyl)ethyl methanesulfonate were added to 80 ml of a solution of 1.35 g of 4-methylamino-l-[4-(1,2,4- triazol-l-yl)benzoyl]piperidine in acetonitrile, at room temperature. The mixture was refluxed by heating, for 5 hours, followed by distillation under reduced pressure to remove the solvent. The residue was extracted with methylene chloride. The extract was washed with water, dried with anhydrous magnesium sulfate, and concen¬ trated. The residue was purified by a silica gel column chromatography (eluant: methylene chloride/methanol = 20/1) and then by a thin-layer chromatography (developer: chloroform/ methanol/ammonia water = 50/10/1). The product was converted into a hydro¬ chloride in ethanol and then treated in ethyl acetate to obtain 0.15 g of 4-{N-methyl-N-[2-(3-pyridyl)ethyl]- amino}-l-[4-(l,2,4-triazol-l-yl)benzoyl]piperidine trihydrochloride as a white amorphous. 'H-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.60-1.91 (2H, m) , 1.91-2.40 (2H, m), 2.79 (3H, d, J=4.2 Hz), 2.65- 3.90 (8H, m), 4.30-4.89 (IH, ), 7.62 (2H, d, J=8.6 Hz), 7.82-8.10 (3H, m) , 8.29 (IH, s), 8.51 (IH, d, J=8.2 Hz), 8.83-8.90 (IH, m) , 8.90-9.01 (IH, m) , 9.40 (IH, s), 11.25-11.58 (IH, m) Using suitable starting materials, the com¬ pounds of Examples 1-106 and 108-262 mentioned above as well as the compounds of Examples 277, 278 and 281-475 mentioned later were obtained in the same manner as in Example 263. Example 264 11.1 ml of benzaldehyde and 10 g of Molecular Sieve 3A were added to 50 ml of a solution of 2.97 g of 4-amino-l-[4-(1,2,4-triazol-l-yl)benzoyl]piperidine in methanol. The mixture was refluxed by heating, for 150 minutes. Thereto was added 4.97 g of sodium borohydride in small portions, under ice-cooling. The mixture was stirred for 1 hour under ice-cooling. The Molecular Sieve 3A was removed by filtration and the filtrate was subjected to distillation to remove the solvent. To the residue was added water. The mixture was made acidic with hydrochloric acid and then washed with ethyl acetate. The aqueous layer was made alkaline with an aqueous sodium hydroxide solution, under ice-cooling, followed by extraction with methylene chloride. The extract was washed with water, dried with anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (eluant: methylene chloride/methanol = 50/1), followed by recrystallization from methylene chloride-ethyl acetate to obtain 2.92 g of 4-benzylamino-l-[4-(1,2,4-triazol-l- yl)benzoyl]piperidine as a white powder. Melting point: 137-138°C Using suitable starting materials, the compounds of the above-mentioned Examples 1-94, 96-146, 148-149, 151-205, 207-212, 217-228 and 230-262 as well as the compounds of below-mentioned Examples 277-278,- 281-312, 317-321, 327-332, 342-378, 381-393, 395-400,. 402-437 and 440-470 were obtained in the same manner as in Example 264. Reference Example 265 0.7 ml of a 37% aqueous formaldehyde solution and 0.21 g of sodium cyanoborohydride were added to 30 ml of a solution of 0.82 g of 4-benzylamino-l-[4-(l,2,4- triazol-l-yl)benzoyl]piperidine in methanol, under ice- cooling. To the mixture was dropwise added 0.7 ml of acetic acid. The mixture was stirred at room tempera- ture for 1 hour and then subjected to distillation to remove the solvent. The residue was extracted with methylene chloride. The extract was washed with a 1 N aqueous sodium hydroxide solution and water, dried with anhydrous magnesium sulfate, and then concentrated. The residue was purified by a silica gel column chromato¬ graphy (eluant: methylene chloride/methanol = 50/1), followed by recrystallization from methylene chloride- diethyl ether to obtain 0.28 g of 4-(N-methyl-N- benzylamino)-l-[4-(l,2,4-triazol-l-yl)benzoyl]piperidine as a white powder. Yield: Melting point: 168-169°C Using suitable starting materials and in the same manner as in Example 265, there were obtained the compounds of the above-mentioned Examples 1, 2, 4-76, 78-88, 90, 92-93, 97-110, 112-123, 125-146, 148-149,- 151-205, 207-212, 217-254 and 256-262 as well as the compounds of below-mentioned Examples 277-278 and 280- 475. Example 266 1.96 ml of methyl isocyanate was dropwise added, with ice-cooling, to 30 ml of a solution of 1.27 g of 4-[N-methyl-N-(2-phenylethyl)amino]-l-(3-methyl-4- amino-5-methoxybenzoyl)piperidine in chloroform. The mixture was stirred at room temperature for 4 hours and then subjected to distillation to remove the solvent. The residue was purified by a silica gel column chromatography (eluant: methylene chloride/methanol = 40/1). The product was converted into an oxalate in ethanol, followed by recrystallization from ethanol- ethyl acetate to obtain 0.43 g of 4-[N-methyl-N-(2- phenylethyl)amino]-l-(3-methyl-4-methylureido-5-methoxy- benzoyl)piperidine oxalate as a white powder. Melting point: 132-133°C Using suitable starting materials and in the same manner as in Example 266, there were obtained the compounds of the above-mentioned Examples 5-7, 9-10, 14-15, 20-23, 35, 40, 53, 55, 118, 125, 132, 135, 140 and 149. Example 267 1.3 g of potassium carbonate was added to a solution of 2.0 g of 4-[N-methyl-N-(2-phenylethyl)- amino]-l-(3-aminobenzoyl)piperidine in 30 ml of acetone and 20 ml of water. Thereto was dropwise added 0.9 ml of 5-chlorovaleryl chloride with ice-cooling. The mixture was stirred at the same temperature for 20 minutes. The reaction mixture was poured into ice water. The mixture was extracted with methylene chloride. The extract was washed with a saturated aqueous sodium chloride solution, dried with magnesium sulfate, and concentrated under reduced pressure to obtain 2.2 g of 4-[N-methyl-N-(2-phenylethyl)amino]-l- [3-(5-chlorovalerylamino)benzoyl]piperidine as a colorless oil. 'H-NMR (200 MHz, CDC1 3 ) δ ppm: 1.30-2.00 (8H, m) , 2.20-2.50 (5H, m) , 2.55-3.20 (7H, ) , 3.40-3.65 (2H, m), 3.65-4.00 (IH, m) , 4.60-4.90 (IH, m), 7.04 (IH, d, J=7.6 Hz), 7.10-7.50 (7H, m) , 7.68 (IH, d, J=7.9 Hz), 8.36 (IH, brs) Using suitable starting materials and in the same manner as in Example 267, there were obtained the compounds of the above-mentioned Examples 17, 36, 52, 57, 59, 60, 63, 74-75, 117, 126, 128, 131, 136-139, 141- 142, 148, 170, 176, 181-184, 186-187, 189-194, 197-201, 204, 207, 210, 213, 215, 217-218, 220-222 and 230 as well as the compounds of below-mentioned Examples 279, 287, 298, 304-305, 311, 314-315, 317, 322, 335, 339-340, 350, 380, 384, 387, 391-392, 394-395, 400, 402-403, 405- 406, 423, 425, 428, 465, 470 and 474. Example 268 230 mg of sodium hydride was added, under ice- cooling, to a solution of 2.2 g of 4-[N-methyl-N-(2- phenylethyl)amino]-1-[3-(5-chlorovalerylamino)benzoyl]- piperidine in 20 ml of dimethylformamide. The mixture was stirred at the same temperature for 30 minutes. The reaction mixture was poured into ice water. The mixture was extracted with methylene chloride. The extract was washed with a saturated aqueous sodium chloride solu- tion, dried with magnesium sulfate, and concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (eluant: methylene chloride/methanol = 100/3 to 20/1) and then converted into a hydrochloride. The hydrochloride was solidified from ethanol-diethyl ether to obtain 1.7 g of 4-[N- methyl-N-(2-phenylethyl)amino]-1-[3-(2-oxo-l-piperidin- yl)benzoyl]piperidine hydrochloride as a white amorphous. Η-NMR (200 MHz, DMS0-d 6 ) δ ppm: 1.50-2.25 (8H, ) , 2.30-2.50 (2H, m) , 2.78 (3H, d, J=4.6 Hz), 3.00- 3.40 (7H, m), 3.50-3.90 (3H, m), 4.35-4.80 (IH, m) , 7.30-7.55 (9H, m) , 10.60-10.90 (IH, m) Example 269 1.0 ml of a 37% aqueous formaldehyde solution, 0.24 g of sodium cyanoborohydride and 0.21 ml of acetic acid were added, in this order, to a solution of 1.0 g of 4-[N-methyl-N-(2-phenylethyl)amino]-l-(4-amino- benzoyl)piperidine in 10 ml of methanol. The mixture was stirred at room temperature for 2 hours. Thereto were added a 37% aqueous formaldehyde solution, sodium cyanoborohydride and acetic acid in this order, each in the same amount as above. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure. To the residue was added 50 ml of ethyl acetate. The mixture was washed with a diluted aqueous sodium hydroxide solution, water and a saturated aqueous sodium chloride solution in this order, dried with sodium sulfate, and concent¬ rated under reduced pressure. The residue was purified by a silica gel column chromatography (eluant: dichloro- methane/methanol = 30/1). The product was converted into a hydrochloride, followed by recrystallization from isopropanol to obtain 0.22 g of 4-[N-methyl-N-(2- phenylethyl)amino]-1-(4-dimethylaminobenzoyl)piperidine hydrochloride as a white powder. Melting point: 220-222°C Using suitable starting materials and in the same manner as in Example 269, there were obtained the compounds of the above-mentioned Examples of 33, 35-36, 41, 46 and 193 as well as the compounds of below- mentioned Examples 299, 386-387, 390, 399, 411, 414-415, 417, 419-421, 423, 430-436, 459, 469 and 471. Example 270 4.72 g of tin chloride was added to 50 ml of a solution of 2.10 g of 4-[N-methyl-N-(2-phenylethyl)- amino]-l-(2-chloro-4-nitrobenzoyl)piperidine in ethanol. The mixture was refluxed by heating, for 1 hour. The reaction mixture was poured into ice water. The mixture was made alkaline with sodium hydroxide and then extracted with chloroform. The extract was washed with water, dried with anhydrous magnesium sulfate, and concentrated. The residue was converted into an oxalate. The oxalate was recrystallized from ethanol- ethyl acetate to obtain 1.94 g of 4-[N-methyl-N-(2- phenylethyl)amino]-1-(2-chloro-4-aminobenzoyl)piperidine oxalate as a white powder. Melting point: 128.5-130°C Using suitable starting materials and in the same manner as in Example 270, there were obtained the compounds of the above-mentioned Examples 62, 64, 113- 114, 116, 127, 130, 167, 179, 188, 192, 202, 209, 211, 219, 241-246, 254 and 257 as well as the compounds of below-mentioned Examples of 283, 292-293, 295, 313, 328, 334, 338, 340, 349, 383, 436, 440-441, 466, 468 and 475. Example 271 24 ml of a 1 N solution of boron tribromide in dichloromethane was dropwise added, at -40°C, to a solu¬ tion of 1.0 g of 4-[N-methyl-N-(2-phenylethyl)amino]-l- [3-methoxy-4-(l,2,4-triazol-l-yl)benzoyl]piperidine in 20 ml of chloroform. The mixture was stirred overnight at that temperature and then returned to room tempera¬ ture. The mixture was cooled to -30°C and 10 ml of methanol was dropwise added thereto. The mixture was poured into ice water. The resulting mixture was made basic with a 25% aqueous sodium hydroxide solution and stirred for a while. The organic layer was separated, water-washed, and concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (eluant: methylene chloride/methanol = 50/1 to 9/1) and then converted into a hydrochloride to obtain 0.42 g of 4-[N-methy1-N-(2-phenylethyl) mino]-l- [3-hydroxy-4-(1,2,4-triazol-l-yl)benzoyl]piperidine hydrochloride as a white amorphous. 'H-NMR (200 MHz, DMS0-d 6 ) δ ppm: 1.55-1.90 (2H, m), 1.90-2.33 (2H, m) , 2.70-3.50 (6H, m) , 2.80 (3H, d, J=4.8 Hz), 3.50-4.00 (2H, m) , 4.35-4.90 (IH, m) , 7.03 (IH, dd, J=1.6 Hz, 8.2 Hz), 7.16 (IH, d, J=1.6 Hz), 7.21-7.44 (5H, m) 7.69 (IH, d, J=8.2 Hz), 8.22 (IH, s), 9.05 (IH, s), 10.30-10.65 (IH, m) , 11.07 (IH, s) Using suitable starting materials and in the same manner as in Example 271, there were obtained the compounds of the above-mentioned Examples of 103, 129, 133-134, 150, 157, 165, 173, 175-178, 213 and 216 as well as the compounds of below-mentioned Examples of 312, 316, 325-326, 359, 362-363, 368-372, 374-378, 381- 383, 385, 390, 393, 397, 401 and 461-468. Example 272 120 mg of sodium hydride was added, under ice- cooling, to a solution of 1.0 g of 4-[N-methyl-N-(2- phenylethyl)amino]-1-[3-hydroxy-4-(1,2,4-triazol-l- yl)benzoyl]piperidine in 10 ml of dimethylformamide. The mixture was stirred for 1 hour. Thereto was dropwise added 320 mg of (2-chloroethyl)dimethylamine. The mixture was stirred at room temperature for 2 hours and then at 50°C for 2 hours. The reaction mixture was poured into 50 ml of water. The mixture was extracted with three 50-ml portions of ethyl acetate. The extract was washed with 50 ml of a saturated aqueous sodium chloride solution, dried with magnesium sulfate, and subjected to distillation to remove the solvent. The residue was purified by a silica gel column chromato¬ graphy (eluant: dichloromethane/methanol = 10/1 to dichloromethane/methanol/ammonia water = 100/10/1). The product was recrystallized from ethyl acetate-n-hexane to obtain 500 mg of 4-[N-methyl-N-(2-phenylethyl)amino]- 1-[3-(2-dimethylaminoethoxy)-4-(1,2,4-triazol-l- yl)benzoyl]piperidine as a white powder. Melting point: 83-85°C Using suitable starting materials and in the same manner as in Example 272, there were obtained the compounds of the above-mentioned Examples 81, 89, 102, 119, 123, 147, 151-152, 159-160, 163, 168, 171, 173, 198, 218, 242, 249-250 and 253. Example 273 1.16 g of 1,2,4-triazole and 1.16 g of potassium carbonate were added to a solution of 2.00 g of 4-[N-methyl-N-(2-phenylethyl)amino]-l-(6-chloro- nicotinoyl)piperidine in 10 ml of dimethyl sulfoxide. The container inside was purged with nitrogen and the container contents were stirred at 100°C for 4 hours. The reaction mixture was cooled and water was added thereto. The mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous sodium chloride solution, dried with anhydrous magnesium sulfate, and concentrated. The residue was purified by a silica gel column chromatography (eluant: methylene chloride/methanol = 150/1). The product was subjected to crystallization from diethyl ether and then to recrystallization from ethyl acetate-diethyl ether to obtain 0.33 g of 4-[N-methyl-N-(2-phenylethyl)amino]-l- [6-(l,2,4-triazol-l-yl)nicotinoyl]piperidine as a white powder. Melting point : 85-86°C Using suitable starting materials and in the same manner as in Example 273, there were obtained the compounds of the above-mentioned Examples 202-204, 219 and 220. Example 274 A solution of 0.63 g of sodium metaperiodate in 5 ml of water was added to a solution of 0.85 g of 4- {N-methyl-N-[2-(4-methylthiophenyl)ethyl]amino}-1-[4- (l,2,4-triazol-l-yl)benzoyl]piperidine in 10 ml of methanol. The mixture was stirred at room temperature for 4 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added ice water. The mixture was made basic with a 25% aqueous sodium hydroxide solution and then extracted with chloroform. The extract was washed with water, dried with sodium sulfate, and concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (eluant: methylene/methanol = 30/1). The product was converted into a hydrochloride and then subjected to crystallization from ethanol-ethyl acetate and further to recrystallization from ethanol- water to obtain 0.13 g of 4-{N-methyl-N-[2-(4- methylsulfinylphenyl)ethyl]amino}-l-[4-(1,2,4-triazol-l- yl)benzoyl]piperidine hydrochloride as a white powder. Melting point: 235-236°C Using suitable starting materials, the compound of the above-mentioned Example 200 was obtained in the same manner as in Example 274. Example 275 51 mg of lithium aluminum hydride was added to a solution of 0.62 g of 4-[N-methyl-N-(2-phenylethyl)- a ino]-1-[3-ethoxycarbonyl-6-(1,2,4-triazol-l-yl)- benzoyl]piperidine in 10 ml of tetrahydrofuran with cooling in an ice-methanol bath. The mixture was stirred for 15 minutes in the same state. A small amount of a saturated aqueous sodium sulfate solution was added carefully, and the mixture was stirred at room temperature for a while. To the reaction mixture were added 10 ml of tetrahydrofuran and sodium sulfate. The mixture was stirred overnight at room temperature. The insolubles were removed by Celite filtration. The filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromato¬ graphy (eluant: methylene chloride/methanol = 9/1). The product was converted into a hydrochloride and then dried under reduced pressure to obtain 0.3 g of 4-[N- methyl-N-(2-phenylethyl)amino]-1-[3-hydroxymethyl-6- (l,2,4-triazol-l-yl)benzoyl]piperidine hydrochloride as a white amorphous. Η-NMR (200 MHz, DMS0-d 6 ) δ ppm: 1.20-2.25 (4H, m) , 2.55-2.90 (4H, m) , 2.90-3.80 (7H, m) , 4.40-4.65 (IH, ), 4.60 (2H, s), 4.80-6.00 (IH, m) , 7.16-7.45 (5H, m), 7.45-7.75 (3H, m) , 8.17 (IH, s), 8.85-9.00 ( IH, m ) , 10 . 60-10 . 93 ( IH, ) Using suitable starting materials, the compound of the above-mentioned Example 201 was obtiained in the same manner as in Example 275. Example 276 45 ml of a saturated solution of ammonia in methanol was added to 600 mg of 4-{N-methyl-N-[2-(4- methoxycarbonylphenyl)ethyl]amino}-l-[4-(l,2,4-triazol- 1-yl)benzoyl]piperidine. The mixture was stirred at 110°C for 69.5 hours in a sealed tube. The reaction mixture was cooled to room temperature and then subjected to distillation to remove the solvent. The residue was purified by a silica gel column chromato¬ graphy (eluant: dichloromethane/methanol/ammonia water = 200/20/1). The product was washed with diethyl ether for crystallization, followed by recrystallization from ethanol to obtain 320 mg of 4-{N-methyl-N-[2-(4-carba- moylphenyl)ethyl]amino}-l-[4-(1,2,4-triazol-l-yl)- benzoyl]piperidine as a white powder. Melting point: 194.5-195.5°C By the method similar to that of employed in Example 276, and by using suitable starting materials, there were obtained compounds of the aobve-mentioned Examples 43 and 98 as well as the compounds of below- mentioned Examples 399, 408-415, 417, 419-421, 430-436, 459 and 471 . By the method similar to that of employed in Example 1 or 3, there were prepared compounds of Examples 277-487 as shown in the following Table 11. ' The NMR data for the compounds of Examples 283 through 485 are shown in the below-mentioned data sheet. Table 11 R-N /-Λ V-N^" R _ 1 (To be continued) Table 11 (Continued ) (To be continued) Table 11 R-N - VN^" R1 . (Continued ) (To be continued) Table 11 (Continued) (To be continued) R Table 11 ■ V N (Continued ) v_y ^R (To be continued) Table 11 (Continued) To be continued) Table 11 R-N VN^ -, ( Continued) v_ ^R 2 Table 11 (Continued) R Table 11 R-N -N: (Continued) R Table 11 ( Continued ) (To be continued) R Table 11 R-N ( Continued) v_y ^R 2 (To be continued) R Table 1 1 R-N -N ( Continued ) ^ R 2 (To be continued) Table 11 (Continued) R - _><! 2 T be ontinued Table 11 ( Continued ) (To be continued) Table 11 (Continued) Table 11 ( Continued) (To be continued) Table 11 (Continued) R - N O< 2 (To be continued) R Table 11 R-N -N y (Continued) R To be continued R Table 11 R-N -N: ( Continued) V 'R To be continued) Table 11 ( Continued ) To be continued Table 11 (Continued) (To be continued) Table 11 (Continued ) R - <R 2 (To be continued) (To be continued) Table 11 (Continued) Table 11 (Continued) Table 11 ( Continued ) : - N O< : (To be continued) Table 11 (Continued) To b inued (To be continued) R Table 11 R -N N y (Continued) v_ • R Table 11 (Continued ) « (To be continued) Table 11 (Continued) (To be continued) Table 11 R -N -N' (Continued) v_ * 2 (To be continued) R Table 11 R (Continued) - N O N: ■ R' (To be continued) R Table 11 R -N -N- (Continued) v__/ • R (To be continued) Table 11 ( Continued) (To be continued) R Table 11 R-N -N y (Continued ) (To be continued) Table 11 (Continued) (To be continued) R' Table 11 R-N -N ^R 2 (Continued ) (To be continued) (To be continued) Table 1 1 ( Continued ) "-O (To be continued) (To be continued) R Table 1 1 R-N V N y ( Continued ) ■ R (To be continued) R Table 11 R-N VN^ ( Continued) • R (To be continued) Table 11 (Continued) (To be continued) Table 11 (Continued) (To be continued) (To be continued) (To be continued) R Table 11 R-N -N y "IT (Continued) (To be continued) R Table 11 R-N Yl (Continued) (To be continued) R Table 11 R-N -N; ( Continued) • R (To be continued) (To be continued) R Table 11 R-N -N (Continued ) ^R 2 To be continued Table 11 R-N VN (Continued ) v_y V R 2 Example No. *H-NMR f200 MHz) δ ppm 283 (250 MHz, DMSO-d 6 ): 1.55-2.00 (2H, m) , 2.00- 2.30 (2H, m), 2.75 (3H, d, J=4.7Hz) , 2.80-3.45 (6H, m), 3.53-3.75 (IH, m) , 3.80-4.80 (2H, m), 6.77 (3H, brs), 7.19-7.43 (6H, ), 7.63 (IH, d, J=8.5Hz), 8.01 (IH, d, J=2.2Hz), 11.00- 11.30 (IH, m) 284 (DMSO-d 6 ): 1.58-1.93 (2H, m) , 1.93-2.39 (2H, m), 2.74 (3H, d, J=4.6Hz), 2.70-2.95 (IH, m), 2.95-3.50 (5H, m) , 3.50-3.90 (2H, m), 4.50- 4.75 (IH, m), 7.10-7.45 (5H, m) , 7.59 (IH, dd, J=7.6Hz, 4.8Hz), 7.69(1H, J=7.6Hz), 8.06 (IH, t, J=7.6Hz), 8.65 (IH, d, J=4.8Hz), 9.00-10.00 (IH, m), 11.20-11.60 (IH, m) 285 (DMSO-d 6 ): 1.60-1.93 (2H, m) , 1.93-2.40 (2H, m), 2.75 (3H, d, J=4.4Hz), 2.65-2.95 (IH, m) , 2.95-3.80 (7H, m) , 4.50-4.75 (IH, m) , 7.15- 7.50 (5H, m), 7.93 (2H, d, J=6.0Hz), 8.93 (2H, d, J=6.0Hz), 8.00-10.00 (IH, m), 11.30-11.70 (IH, m) 286 (250 MHz, DMSO-d 6 ): 1.56-1.90 (2H, m), 1.90- 2.40 (2H, m), 2.52 (3H, s), 2.76 (3H, d, J=4.7Hz), 2.69-2.95 (IH, m) , 3.0-3.50 (6H, m) , 3.55-3.80 (IH, m) , 4.55-4.80 (IH, m), 7.20- 7.50 (6H, m), 7.67 (IH, d, J=6.2Hz), 8.54 (IH, dd, J=6.2Hz, 1.7Hz), 11.20-11.53 (IH, m) 287 (250 MHz, DMSO-d 6 ): 1.08 (3H, t, J=7.5Hz), 1.50-1.87 (2H, m), 1.90-2.30 (2H, m) , 2.38 (2H, q, J=7.5Hz), 2.75 (3H, d, J=4.5Hz) , 2.65- 2.90 (IH, m), 2.90-3.50 (5H, ), 3.50-3.70 (IH, m), 3.95-4.18 (IH, m), 4.50-4.70 (IH, ih), 4.70-6.00 (IH, m), 7.20-7.44 (5H, ) , 7.59 (IH, d, J=8.5Hz), 8.17 (IH, d, J=8.5Hz), 8.79 (IH, s), 10.48 (IH, s), 10.65-11.30 (IH, m) 289 (DMSO-d 6 ): 1.59-2.34 (4H, m) , 2.65 (3H, s), 2.76 (3H, d, J=4.2Hz), 2.70-3.00 (IH, m), 3.00-3.70 (7H, ), 4.50-4.75 (IH, m) , 7.18- 7.46 (5H, ), 7.68 (IH, dd, J=4.9Hz, 1.6Hz), 7.91 (IH, d, J=1.6Hz), 8.81 (IH, d, J=4.9Hz) , 10.50-11.70 (IH, m) 290 (DMSO-d 6 ): 1.60-2.00 (2H, m) , 2.00-2.35 (2H, m), 2.44 (3H, s), 2.61 (3H, s), 2.76 (3H, d, J=4.40Hz), 2.70-2.98 (IH, m) , 2.98-3.55 (5H, m) , 3.55-3.75 (IH, m) , 3.75- 4.17 (IH, m), 4.50-4.80 (IH, m) , 7.10-7.50 (5H, m), 7.70 (IH, s), 7.86 (IH, s), 10.90-11.20 (IH, m) 291 (DMSO-d 6 ): 1.52-1.87 (2H, ) , 1.95-2.23 (2H, m), 2.75 (3H, d, J=4.2Hz) , 2.32-3.49 (7H, m) , 3.49-3.75 (IH, m) , 3.95-5.20 (3H, m) , 6.34 (IH, d, J=9.4Hz), 7.20-7.50 (5H, ) , 7.49 (IH, dd, J=9.4Hz, 2.6Hz), 7.58 (IH, d, J=2.6Hz), 10.65-11.25(1H, m) 294 (DMSO-d 6 ): 1.49-1.88 (2H, m) , 1.91-2.22 (2H, ), 2.22 (3H, s), 2.77 (3H, d, J=4.5Hz) , 2.77- 3.45 (6H, ), 3.45-3.60 (IH, m) , 3.52 (2H, s), 3.80-4.70 (2H, m) , 7.10 (2H, d, J=3.0Hz), 7.20-7.50 (5H, m) , 10.62 (IH, s), 10.88-11.12 (IH, m) 296 (DMSO-d 6 ): 1.42-1.90 (2H, m) , 1.90-2.49 (2H, m), 2.62-2.43 (4H, m) , 2.43-3.89 (7H, ) , 4.42-4.80 (IH, m) , 6.04-6.43 (IH, m), 7.15- 7.75 (7H, m), 11.0-11.40 (IH, m) , 11.80-12.30 (IH, m) 297 (DMSO-d 6 ): 1.60-1.95 (2H, m) , 1.95-2.39 (2H, m), 2.40-3.52 (6H, m) , 2.59 (3H, s), 2.75 (3H, d, J=4.6Hz), 3.52-4.00 (2H, m) , 4.20-5.60 (2H, m), 7.19-7.42 (5H, m) , 7.54 (IH, d, J=8.0 Hz), 7.99 (IH, dd, J=8.0 Hz, 1.8 Hz), 8.63 (IH, d, J=1.8 Hz), 11.28-11.52 (IH, m) 298 (DMSO-d 6 ): 1.12 (3H, t, J=7.6 Hz), 1.60-1.92 (2H, m), 1.92-2.35 (2H, m) , 2.46 (2H, q, J=7.6Hz), 2.52 (3H, s), 2.78 (3H, d, J=4.4Hz) , 2.80-2.95 (IH, m) , 2.95-3.50 (5H, m) , 3.50- 3.80 (IH, m), 3.80-4.05 (IH, m), 4.50-4.80 (IH, m), 6.35 (IH, brs), 7.19-7.47 (5H, m), 7.52 (IH, d, J=8.4Hz), 8.13 (IH, d, J=8.4 Hz), 9.74 (IH, s), 11.06-11.31 (IH, m) 299 (DMSO-d 6 ): 1.11 (3H, t, J=7.2Hz) , 1.55-1.92 (2H, m), 1.92-2.36 (2H, m) , 2.58-2.95 (4H, m) , 2.95-3.50 (7H, m) , 3.50-3.80 (2H, m) , 4.46- 4.74 (IH, m), 7.10-7.70 (6H, m) , 7.97-8.20 (2H, m), 8.67 (IH, s), 8.80-8.99 (IH, m), 11.20-11.50 (IH, m) 305 (DMSO-d 6 ): 1.10 (3H, t, J=7.4Hz), 1.49-1.90 (2H, m), 1.90-2.32 (2H, m), 2.27 (3H, s), 2.41 (2H, q, J=7.4Hz), 2.75 (3H, d, J=4.2Hz) , 2.60- 2.95 (IH, m), 2.95-3.49 (5H, m) , 3.49-3.80 (IH, m), 3.90-4.05 (IH, m) , 4.50-4.72 (IH, m) , 7.12-7.43 (5H, m) , 7.50 (IH, s), 8.60 (IH, s), 9.68 (IH, s), 10.86-11.20 (IH, m) 306 (DMSO-d 6 ): 1.55-1.90 (2H, m) , 1.91-2.29 (2H, m) , 2.60-3.48 (12H, m) , 3.59 (2H, s), 3.48- 4.72 (IH, m), 3.72-4.82 (2H, m) , 7.02 (IH, d, J=8 . 0Hz )J 7.20-7.55 (7H, m) , 10.88-11.12 (IH, m) 307 (DMSO-d 6 ): 1.49-1.85 (2H, m) , 1.85-2.36 (2H, m), 2.22 (3H, s), 2.69-2.87 (3H, ) , 2.87-3.90 (8H, m), 3.43 (2H, s), 4.27-4.86 (IH, m) , 6.83 (IH, d, J=8.0Hz), 7.05 (IH, d, J=8.0Hz), 7.16- 7.51 (5H, m), 10.58 (IH, s), 10.89-11.20 (IH, m) 308 (DMSO-d 6 ): 1.33 (3H, d, J=7.5Hz), 1.54-1.90 (2H, m), 1.95-2.30 (2H, ) , 2.70-2.84 (3H, m) , 2.84-3.72 (10H, m), 3.72-4.70 (2H, ) , 6.87 (IH, d, J=8.0Hz), 7.15-7.48 (7H, m) , 10.58 (IH, s), 10.92-11.22 (IH, m) 309 (DMSO-d 6 ): 1.51-1.90 (2H, m) , 1.95-2.22 (2H, m), 2.28 (3H, s), 2.77 (3H, d, J=4.2Hz) , 2.65- 3.48 (6H, m), 3.48-3.70 (IH, m) , 3.75-4.75 (2H, m), 6.81 (IH, s), 6.84 (IH, s), 7.20-7.50 (5H, m), 10.77 (IH, s), 10.93 (IH, s), 10.90-11.25 (IH, m) 310 (DMSO-d 6 ): 1.50-1.91 (2H, ) , 1.90-2.30 (2H, m), 2.77 (3H, d, J=4.4Hz) , 2.65-3.48 (6H, m), 3.48-3.74 (IH, m) , 3.85 (3H, s), 3.90-4.70 (2H, m) , 6.65 (IH, s), 6.70 (IH, s), 7.17-7.43 (5H, m) , 10.79 (IH, s), 10.93 (IH, s), 10.95-11.25 (IH, m) 313 (DMSO-d 6 ): 1.40-1.95 (2H, m) , 1.95-2.41 (2H, m), 2.71 (3H, d, J=4.4Hz), 2.61-3.57 (6H, m) , 3.57-3.95 (2H, m) , 4.05-4.40 (IH, m) , 4.45- 4.84 (IH, m), 4.83-5.70 (3H, brs), 6.73 (IH, d, J=8.0Hz), 6.95 (IH, s), 7.10-7.30 (4H, m) , 7.34 (IH, d, J=8.0Hz), 8.03 (IH, s), 8.95 (IH, s), 11.30-11.90 (IH, ) 300 (DMSO-d 6 ): 1.55-1.93 (2H, m) , 1.93-2.40 (2H, m), 2.74 (3H, d, J=4.4Hz) , 2.65-2.95 (IH, m) , 2.95-3.80 (7H, m) , 4.55-4.75 (IH, ) , 7.13- 7.45 (5H, m), 7.50-7.66 (IH, m) , 7.78 (IH, d, J=8.2Hz), 8.20 (IH, d, J=4.8Hz) , 9.10-10.30 (IH, brs), 11.0-12.0 (IH, m), 11.05-11.27 (IH, brs) 304 (DMSO-d 6 ): 1.12 (3H, t, J=7.5Hz), 1.50-1.90 (2H, m), 1.90-2.30 (2H, ), 2.24 (3H, s), 2.40 (2H, q, J=7.5Hz), 2.42 (3H, s), 2.64-2.93 (4H, m), 2.93-3.50 (5H, m), 3.50-3.75 (IH, ), 3.75-3.95 (IH, ), 4.50-4.72 (IH, m) , 5.70- 6.70 (IH, brs), 7.15-7.42 (5H, m) , 7.49 (IH, s), 9.83 (IH, s), 10.95-11.25 (IH, m) 316 (DMSO-d 6 ): 1.50-2.36 (4H, m) , 2.72 (3H, d, J=4.4Hz), 2.60-3.55 (6H, m), 3.55-4.00 (2H, m), 4.10-4.42 (IH, m), 4.42-4.83 (IH, m), 7.04 (IH, d, J=8.0Hz), 7.11-7.38 (5H, m) , 7.69 (IH, d, J=8.0Hz), 8.21 (IH, s), 9.05 (IH, s), 11.11 (IH, s), 11.25-11.63 (IH, πi) 317 (DMSO-d 6 ): 1.12 (3H, t, J=7.6Hz), 1.55-1.90 (2H, m), 1.93-2.28 (2H, ), 2.15 (6H, s), 2.34 (2H, q, J=7.6Hz), 2.58-3.30 (2H, ) , 2.81 (3H, s), 3.35-4.10 (6H, m), 4.35-4.95 (IH, m), 5.95 (IH, brs), 7.11 (2H, s), 7.63-7.77 (IH, m), 7.82 (IH, d, J=7.8Hz) , 8.20-8.35 (IH, m), 8.68-8.80 (IH, m) , 9.33 (IH, s), 11.12 (IH, brs) 318 (DMSO-d 6 ): 1.35-1.81 (2H, m) , 1.81-2.30 (2H, m), 2.08 (3H, s), 2.68-2.85 (3H, m) , 2.85-3.73 (8H, m) , 3.45 (2H, s), 4.51-4.81 (IH, m), 6.69 (IH, d, J=8.0Hz) , 6.84-7.19 (IH, m), 7.19-7.46 85H, m), 10.47 (IH, s), 10.35-10.69 (IH, m) 319 (DMSO-d 6 ): 1.35-1.83 (2H, ) , 1.83-2.38 (2H, m), 2.16 (3H, s), 2.68-2.88 (3H, m) , 2.88-3.07 (8H, m), 3.44 (2H, s), 4.50-4.80 (IH, m), 6.69 (IH, s), 6.87-7.19 (IH, m) , 7.19-7.50 (5H, m) , 10.48 (IH, s), 10.64-10.91 (IH, m) 321 (DMSO-d 6 ): 1.41-1.79 (2H, ) , 1.79-2.25 (2H, m), 2.65-2.80 (3H, m) , 2.80-3.69 (8H, m) , 4.49-4.77 (IH, m) , 4.71 (IH, s), 6.83-7.40 (7H, m), 7.50-10.35 (2H, m) , 11.11 (IH, s) 325 (DMSO-d 6 ): 1.53-2.40 (4H, m) , 2.71 (3H, d, ' J=4.4Hz), 2.55-3.49 (6H, m) , 3.50-3.98 (2H, m), 4.02-4.36 (IH, m) , 4.40-4.90 (IH, m) , 6.50-6.72 (2H, m), 7.0 (IH, d, J=8.0Hz), 7.64 (2H, d, J=8.60Hz), 7.95 (2H, d, J=8.6Hz), 8.27 (IH, s), 9.31 (IH, s), 9.37 (IH, s), 11.02- 11.50 (IH, m) 327 (DMSO-d 6 ): 1.30-2.08 (3H, m) , 2.08-2.36 (IH, m), 2.77 (3H, s), 2.65-3.80 (8H, m) , 4.50-4.77 (IH, m) , 6.80-7.17 (IH, m) , 7.17- 7.45 (5H, m), 7.69 (IH, s), 10.70-11.17 (IH, m), 11.39 (IH, s), 11.64 (IH, s) 328 (DMSO-d 6 ): 1.55-1.95 (2H, m), 1.95-2.20 (2H, m), 2.78 (3H, s), 2.68-3.80 (10H, m) , 3.95-4.36 (2H, m) , 6.63 (IH, s), 6.72 (IH, s), 7.18-7.45 (5H, m) , 10.48 (IH, s), 10.64 (IH, s), 10.66 (IH, brs) 329 (DMSO-d 6 ): 1.45-1.82 (2H, m) , 1.82-2.30 (2H, m), 2.76 (3H, d, J=4.5Hz) , 2.91-3.75 (8H, m), 3.52 (2H, s), 4.30-4.85 (IH, m) , 6.94 (IH, d, J=8.5Hz), 7.15-7.50 (6H, m) , 10.55- 10.79 (IH, m), 10.95 (IH, s) 330 (DMSO-d 6 ): 1.44-1.85 (2H, m) , 1.85-2.34 (2H, m), 2.76 (3H, d, J=4.5Hz) , 2.93-3.84 (10H, ), 4.30-4.87 (IH, m) , 6.78-7.00 (2H, m), 7.11-7.49 (6H, m), 10.55 (IH, s), 10.78-11.06 (IH, m) 331 (DMSO-d 6 ): 1.46-1.83 (2H, m) , 1.89-2.25 (2H, m), 2.75 (3H, d, J=4.5Hz) , 2.65-3.70 (7H, m), 3.43 (2H, s), 3.83 (3H, s), 3.70-5.02 (2H, m), 6.80-7.05 (2H, ) , 7.12-7.45 (5H, m) , 10.54 (IH, s), 10.75-11.05 (IH, m) 332 (DMSO-d 6 ): 1.26 (6H, s), 1.51-1.89 (2H, m) , 1.92-2.25 (2H, m) , 2.68-2.84 (3H, m) , 2.84- 3.49 (6H, m), 3.49-3.71 (IH, m) , 3.71-4.80 (2H, m), 6.88 (IH, d, J=8.0Hz), 7.11-7.48 (7H, ), 10.55 (IH, s), 10.75-11.02 (IH, m) 334 (DMSO-d 6 ): 1.50-2.40 (4H, m), 2.70 (3H, s), 2.60-3.99 (8H, m) , 4.09-4.43 (IH, m) , 4.43-4.91 (IH, m) , 7.09-7.25 (2H, m) , 7.29 (IH, d, J=8.0Hz), 7.38-7.53 (5H, m) , 9.32- 10.90 (3H, brs), 11.30-12.20 (IH, brs) 335 (DMSO-d 6 ): 1.12 (3H, t, J=7.6Hz) , 1.50-1.98 (2H, m), 1.98-2.45 (2H, m) , 2.15 (6H, ) , 2.34 (2H, q, J=7.6Hz), 2.58-4.00 (8H, ) , 2.72 (3H, s), 4.19-4.95 (2H, m) , 7.12 (2H, s), 7.52 (IH, d, J=8.0Hz), 8.02-8.20 (2H, m) , 9.31 (IH, s), 11.60-12.00 (IH, m) 337 (DMSO-d 6 ): 1.30-1.93 (2H, m) , 1.93-2.29 (2H, m), 2.01 (3H, s), 2.40-2.25 (IH, m) , 2.66 (3H, d, J=4.3Hz), 3.00-3.24 (IH, m) , 3.24-3.79 (5H, m), 3.88-4.08 (IH, m), 4.26-4.48 (IH, m) , 4.48-4.61 (IH, m), 7.48-7.62 (IH, m) , 8.08- 8.21 (2H, m), 11.40-11.85 (IH, m) 338 (DMSO-d 6 ): 1.30-2.34 (5H, m), 2.01 (3H, s), 2.40-2.72 (IH, m) , 2.64 (3H, s), 2.90-3.54 (4H, m), 3.54-3.77 (IH, m) , 3.85-4.05 (lH, ' m), 4.12-4.40 (IH, m), 4.40-4.60 (IH, m), 7.17 (IH, d, J=7.9Hz), 7.22 (IH, s), 7.32 (IH, d, J=7.9Hz), 9.30-11.10 (3H, brs), 11.50-11.92 (IH, m) 339 (DMSO-d 6 ): 1.55-2.40 (4H, m) , 2.01 (3H, s), 2.72 (3H, d, J=4.4Hz), 2.60-3.90 (8H, m) , 4.10-4.39 (IH, m), 4.39-4.88 (IH, m) , 7.14 (IH, d, J=8.2Hz), 7.30-7.44 (IH, m) , 7.50-7.60 (IH, ), 7.64 (2H, d, J=8.4Hz), 7.95 (2H, d, J=8.4Hz), 8.27 (IH, s), 9.37 (IH, s), 9.95 (IH, s), 11.18-11.55 (IH, m) 341 (DMSO-d 6 ): 1.55-2.32 (4H, m) , 2.57-4.00 (8H, m), 2.72 (3H, s), 4.12-4.38 (IH, s), 4.95-4.89 (IH, m), 7.07 (IH, d, J=7.8Hz), 7.12 (IH, s), 7.27 (IH, d, J=7.8Hz), 7.64 (2H, d, J=8.6Hz), 7.95 (2H, d, J=8.6Hz), 8.27 (IH, s), 9.38 (IH, s), 8.90-10.50 (3H, brs), 11.34-11.80 (IH, m) 344 (DMSO-d 6 ): 1.55-1.94 (2H, m), 1.94-2.39 (2H, m), 2.54-3.94 (8H, m), 2.77 (3H, d, J=4.4Hz) , 4.48-4.85 (IH, m) , 7.20-7.43 (5H, m ) , 7.57 (2H, d, J=8.2Hz), 7.85 (2H, d, J=8.2Hz), 7.99 (2H, d, J=9.0Hz), 8.31 (2H, d, J=9.0Hz), 11.18-11.52 (IH, m) 349 (DMSO-d 6 ): 1.55-2.90 (2H, m), 1.96-2.35 (2H, m), 2.65-3.50 (6H, m) , 2.77 (3H, s), 3.50-4.20 (2H, m), 4.27-4.99 (IH, m) , 7.18-7.45 (5H, m) , 7.39 (2H, d, J=8.4Hz), 7.51 (2H, d, J=8.2Hz), 7.66-7.83 (4H, m) , 8.10-11.00 (3H, brs), 11.00-11.30 (IH, m) 352 (DMSO-d 6 ): 1.33 (3H, d, J=8.0Hz), 1.50-1.90 (2H, m), 1.90-2.29 (2H, m) , 2.75 (3H, d, J=4.0Hz), 2.83-3.10 (2H, m), 3.10-3.75 (6H, ), 3.75-4.68 (2H, m) , 6.85 (IH, d, J=8.0Hz), 6.92-7.10 (2H, m) , 7.20-7.32 (IH, m) , 7.32- 7.39 (IH, m), 7.39-7.49 (IH, m) , 10.55 (IH, s), 10.82-11.14 (IH, m) 353 (DMSO-d 6 ): 1.59-1.92 (2H, m) , 1.92-2.35 (2H, m), 269-283 (3H, m), 2.83-2.99 (IH, m), 2.99- 3.50 (5H, m), 3.50-3.86 (2H, m), 3.86-4.11 (IH, m), 4.56-4.81 (IH, m) , 7.16-7.40 (5H, m), 7.40-7.65 (4H, m) , 7.91-8.20 (4H, m) , 10.75- 11.08 (IH, m) 354 (DMSO-d 6 ): 1.59-1.92 (2H, m) , 1.98-2.39 (2H, m), 2.76 (3H, d, J=4.5Hz), 2.81-2.97 (IH, m) , 2,97-3.49 (5H, m) , 3.49-3.76 (IH, m) , 3.76- 4.14 (2H, m), 4.51-4.80 (IH, m) , 7.17-7.38 (5H, m), 7.38-7.62 (3H, m) , 7.70 (IH, d, J=8.0Hz), 7.75-7.87 (2H, m) , 8.23 (IH, dd, J=8.0Hz, 2.5Hz), 8.90 (IH, d, J=2.5Hz), 10.95- 11.25 (IH, m) 362 (DMSO-d 6 ): 1.55-1.90 (2H, m), 1.95-2.28 (2H, m), 2.79 (3H, d, J=4.0Hz) , 2.70-3.50 (6H, m) , 3.50-4.26 (2H, m) , 4.26-490 (IH, m) , 6.84 (IH, d, J=8.2Hz), 6.98 (IH, dd, J=8.2Hz, 2.2Hz) , 7.08 (IH, d, J=2.2Hz), 7.20-7.42 (5H, m) , 7.45 (2H, d, J=8.4Hz), 7.59 (2H, d, J=8.4Hz), 9.11 (IH, s), 9.19 (IH, s), 10.55-11.84 (IH, m) 363 (DMSO-d 6 ): 1.55-1.90 (2H, m) , 1.94-2.30 (2H, m), 2.60-3.50 (6H, m), 2.78 (3H, d, J=4.4Hz), 3.50-3.73 (IH, m) , 3.73-4.83 (2H, m) , 6.80 (2H, d, J=8.6Hz), 6.87 (IH, d, J=7.6Hz), 6.98 (IH, s), 7.19-7.48 (8H, m) , 9.48 (IH, s), 9.79 (IH, s), 10.81-11-10 (IH, m) 366 (DMSO-d 6 ): 1.55-1.92 (2H, m) , 1.92-2.35 (2H, m), 2.68-2.89 (3H, m) , 2.89-3.50 (7H, m) , 3.50-4.02 (IH, m), 3.69 (3H, s), 3.70 (3H, s), 3.78 (3H, s), 4.25-487 (IH, m), 6.55 (IH, dd, J=8.5Hz, 2.5Hz), 6.62 (IH, d, J=2.5Hz), 6.93- 7.12 (3H, m), 7.15 (IH, d, J=7.5Hz), 7.33-7.49 (5H, m), 10.85-11.19 (IH, m) 369 (DMSO-d 6 ): 1.56-1.90 (2H, m) , 1.95-2.34 (2H, m), 2.65-3.50 (7H, m) , 2.77 (3H, d, J=4.4Hz) , 3.50-4.18 (2H, m) , 3.77 (3H, s), 4.18-4.86 (IH, m), 6.83-7.05 (4H, m) , 7.18-7.42 (6H, m) , 7.50 (2H, d, J=8.8Hz), 9.91 (IH, s), 10.85- 11.20 (IH, m) 371 (DMSO-d 6 ): 1.50-1.90 (2H, m) , 1.95-2.30 (2H, m), 2.79 (3H, d, J=3.8Hz), 2.65-3.52 (6H, m) , 3.52-3.74 (IH, m) , 3.74-4.18 (IH, m) , 4.18- 4.80 (IH, m), 6.70-7.00 (4H, m) , 7.03 (IH, d J=1.8Hz), 7.21 (IH, d, J=7.8Hz), 7.25-7.43 (5H, m), 8.93 (IH, s), 8.95 (IH, s), 9.75 (IH, s), 10.65-10.95 (IH, m) 378 (DMSO-d 6 ): 1.51-1.90 (2H, m) , 1.90-2.30 (2H, m), 2.70-2.85 (3H, m) , 2.85-3.50 (6H, m), 3.50-3.73 (IH, m) , 3.73-4.20 (IH, m) , 4.20- 4.95 (IH, m), 6.26 (IH, dd, J=8.5Hz, 2.5Hz) , 6.35 (IH, d, J=2.5Hz), 6.78-6.89 (IH, m) , 6.89-7.02 (2H, m) , 7.15 (IH, d, J=8.0Hz), 7.20-7.47 (5H, m), 9.10-9.48 (3H, m) , 10.58- 10.85 (IH, ) 381 (DMSO-d 6 ): 0.26-0.14 (0.7H, m) , 0.77-1.20 (0.7Hz), 1.20-2.20 (2.6H, m), 2.20-2.48 (3H, m), 2.55-3.55 (8H, m) , 4.46-4.78 (IH, m) , 6.81 (0.8H, d, J=8.6Hz), 6.91 (1.2H, d, J=8.6Hz), 7.17 (0.8H, d, J=8.6Hz), 7.20-7.55 (10.2H, m) , 9.65 (0.4H, ε), 9.75 (0.3H, s), 9.78 (0.3H, s), 10.55-10.90 (IH, m) 385 (DMSO-d 6 ): 1.60-1.91 (2H, m) , 1.96-2.33 (2H, m), 2.83 (3H, d, J=3.6Hz), 2.66-.3.25 (2H, m), 3.30-4.18 (4H, m) , 4.18-4.90 (3H, ) , 6.88 (2H, d, J=8.4Hz), 6.96-7.10 (3H, m) , 7.25-7.42 (2H, m), 7.46 (2H, d, J=8.4Hz), 7.54 (2H, d, J=8.4Hz), 7.65 (2H, d, J=8.4Hz), 9.69 (IH, s), 10.65-10.90 (IH, m) 386 (DMSO-d 6 ): 1.55-1.90 (2H, m) , 1.90-2.34 (2H, m), 2.60-3.34 (4H, m) , 2.75 (3H, ε), 2.92 (3H, s), 3.50-4.06 (4H, m) , 4.30-4.89 (IH, m) , 6.68 (IH, t, J=7.2Hz), 6.85 (2H, d, J=8.0Hz) , 7.19 (2H, dd, J=7.2Hz, 8.0Hz), 7.61 (2H, d, J=8.6Hz), 7.94 (2H, d, J=8.6Hz) , 8.27 (IH, s), 9.38 (IH, ε), 11.15-11.43 (IH, m) 387 (DMSO-d 6 ): 1.11 (3H, t, J=7.6Hz), 1.50-1.90 (2H, m), 1.96-2.29 (2H, ), 2.14 (6H, ε), 2.33 (2H, q, J=7.6Hz), 2.60-3.40 (4H, m) , 2.74 (3H, ε), 2.91 (3H,ε), 3.45-4.11 (4H, m) , 4.25-5.20 (2H, m), 6.68 (IH, t, J=7.2Hz), 6.86 (2H, d, J=8.2Hz), 7.09 (2H, ε), 7.19 (2H, dd, J=7.2Hz), 9.34 (IH, 8), 11.19-11.49 (IH, m) 388 (DMSO-d 6 ): 1.47-1.86 (2H, m) , 1.86-2.30 (2H, m), 2.41-4.03 (8H, m), 2.69 (3H, s), 4.30-4.90 (IH, m), 7.60 (2H, d, J=8.5Hz), 7.94 (2H, d, J=8.5Hz), 7.72-9.75 (4H, m) , 8.26 (IH, s), 9.39 (IH, s) 390 (DMSO-d 6 ): 1.58-1.92 (2H, m) , 1.92-2.38 (2H, m), 2.57-3.40 (4H, m) , 2.76 (3H, ε), 2.91 (3H, ε), 3.45-4.03 (4H, m) , 4.20-5.10 (2H, m), 6.68 (IH, t, J=7.2Hz), 6.80-6.95 (4H, m) , 7.15-7.30 (2H, ), 7.44 (2H, d, J=8.2Hz) , 7.52 (2H, d, J=8.6Hz), 7.63 (2H, d, J=8.2Hz), 10.95-11.12 (IH, m) 391 (DMSO-d 6 ): 1.50-1.92 (2H, m), 1.69 (3H, ε), 1.92-2.28 (2H, m) , 2.61-4.00 (8H, m) , 2.72 (3H, d, J=4.2Hz), 4.40-4.88 (IH, m) , 7.61 (2H, d, J=8.6Hz), 7.94 (2H, d, J=8.6Hz) , 8.21-8.42 (IH, m), 8.27 (IH, ε), 9.37 (IH, s), 10.55- 10.85 (IH, m) 396 (DMSO-d 6 ): 0.70-1.40 (6H, m) , 1.40-1.89 (9H, m), 1.89-2.29 (2H, m), 2.38-3.32 (4H, m) , 2.64 (3H, d, J=4.2Hz), 3.35-3.95 (2H, m), 4.39-4.82 (IH, m), 7.61 (2H, d, J=8.4Hz), 7.95 (2H, d, J=8.4Hz), 8.27 (IH, s), 9.39 (IH, s), 10.75- 11.05 (IH, m) 401 (DMSO-d 6 ): 1.50-1.93 (2H, m) , 1.93-2.37 (2H, )-, 2.58-3.28 (7H, m) , 3.28-3.89 (5H, m) , 4.15-4.80 (2H, ) , 6.32 (IH, dd, J=8.5Hz, 2.5Hz), 6.45 (IH, d, J=2.5Hz), 7.09 (IH, d, J=8.5Hz), 7.16-7.47 (7H, m) , 7.47-7.64 (2H, m), 9.19-9.80 (3H, m) 399 (DMSO-d 6 ): 1.12 (3H, t, J=7.2Hz), 1.55-1.90 (2H, m), 1.90-2.33 (2H, ) , 2.61-3.86 (10H, m), 2.76 (3H, d, J=4.4Hz) , 4.32-4.95 (IH, m) , 7.18-7.40 (5H, m) , 7.48 (2H, d, J=8.2Hz), 7.89 (2H, d, J=8.2Hz), 8.50-8.65 (IH, ) , 10.81- 11.08 (IH, m) 405 (DMSO-d 6 ): 1.10 (3H, t, J=7.5Hz), 1.31-1.84 (2H, m), 1.91-2.20 (2H, m) , 1.99 (3H, s), 2.09 (6H, s), 2.30 (2H, q, J=7.5Hz), 2.72 (3H, d, J=4.0Hz), 2.85-3.41 (6H, m) , 3.41-3.66 (IH, m), 3.80-4.07 (IH, m) , 4.32-4.69 (IH, m) , 6.98 (2H, s), 9.15 (IH, s), 10.50-10.81 (IH, m) 411 (DMSO-d 6 ): 1.11 (3H, t, J=7.0Hz) , 1.55-1.89 (2H, m), 1.89-2.32 (2H, m) , 2.66-2.90 (3H, m), 2.90-3.20 (IH, m) , 3.20-3.40 (2H, m), 3.40-3.80 (6H, m) , 4.42-4.78 (IH, m) , 4.78- 6.49 (2H, m), 7.40-7.57 (2H, m) , 7.57-7.72 (IH, m), 7.72-7.84 (IH, m) , 7.84-7.98 (2H, m) , 8.11-8.30 (IH, ), 8.51-8.65 (IH, m) , 8.65- 8.77 (IH, m), 11.02-11.35 (IH, m) 418 (DMSO-d 6 ): 1.55-1.90 (2H, m) , 1.90-2.35 (2H, m), 2.69-3.50 (6H, m), 2.78 (3H, d, J=4.4Hz), 3.50-3.80 (2H, m) , 4.40 (2H, s), 4.48-4.91 (IH, m), 7.18-7.42 (5H, m), 7.50 (IH, d, J=7.6Hz), 7.60 (IH, s), 7.72 (IH, d, J=7.6Hz), 8.68 (IH, s), 10.50-10.80 (IH, m) 423 (DMSO-d 6 ): 1.09 (3H, t, J=7.4Hz), 1.55-1.90 (2H, m), 2.20-2.25 (2H, m) , 2.38 (2H, q, J=7.4Hz), 2.78 (3H, d, J=4.4Hz) , 2.97-3.52 (6H, m), 3.52-3.75 (IH, m) , 4.33-4.55 (2H, m) , 6.60 (IH, d, J=4.0Hz), 7.21 (IH, d, J=4.0Hz), 7.26-7.45 (5H, ), 10.45-10.65 (IH, m), 11.46 (IH, s) 428 (DMSO-d 6 ): 1.06 (3H, t, J=7.6Hz), 1.50-1.93 (2H, m), 2.00-2.26 (2H, m) , 2.42 (2H, q, J=7.6Hz), 2.77 (3H, d, J=4.4Hz) , 2.84-3.50 (6H, m), 3.50-3.78 (IH, m), 3.80-4.60 (2H, m), 7.90 (IH, d, J=5.8Hz), 7.03 (IH, d, J=5.8Hz) , 7.18-7.43 (5H, m) , 10.62 (IH, s), 10.90-11.13 (IH, m) 433 (DMSO-d 6 ): 1.09 (3H, t, J=7.2Hz), 1.55-1.90 (2H, m), 1.90-2.38 (2H, m), 2.65-2.98 (IH, m) , 2.76 (3H, d, J=4.4Hz), 2.98-3.51 (7H, m) , 3.51-3.78 (2H, m), 3.88 (3H, s), 4.45-4.82 (IH, m), 7.03 (IH, d, J=7.6Hz), 7.11 (IH, s), 7.19-7.47 (5H, m), 7.71 (IH, d, J=7.6Hz), 8.20 (IH, t, J=5.6Hz), 10.85-11.23 (IH, m) 436 (DMSO-d 6 ): 1.12 (3H, t, J=7.1Hz), 1.39-1.85 (2H, m), 1.85-2.38 (2H, m), 2.65-2.89 (IH, m) , 2.75 (3H, s), 2.89-3.48 (8H, m) , 3.48-3.75 (IH, m), 3.83 (1.8H, s), 3.87 (1.2H, s), 4.52-4.79 (IH, m) , 7.18-7.42 (6H, m) , 7.42- 7.60 (2H, m), 8.54-8.69 (IH, m) , 10.62-11.06 (IH, m) 345 (DMSO-d 6 ): 1.33 (3H, d, J=7.5Hz), 1.54-1.89 (2H, m), 1.95-2.30 (2H, m) , 2.72-2.85 (3H, m), 2.85-3.19 (2H, m) , 3.30-3.78 (6H, m) , 3.78- 5.22 (3H, m), 6.86 (IH, d, J=8.OHz) , 7.16-7.42 (2H, m), 7.60-7.73 (IH, m) , 7.73-7.89 (IH, m), 8.11-8.34 (IH, m), 8.62-8.80 (IH, m), 10.56 (IH, s), 11.05-11.35 (IH, m) 346 (DMSO-d 6 ): 1.50-1.83 (2H, m), 1.89-2.25 (2H, m), 2.69-3.18 (4H, m), 3.24-4.71 (11H, m) , 3.83 (3H, s), 6.85-7.04 (2H, m) , 7.50-7.65 (IH, m), 7.65-7.78 (IH, m) , 8.01-8.22 (IH, m) , 8.60-8.74 (IH, m) , 10.54 (IH, s), 10.70-11.02 (IH, m) 437 (DMSO-d 6 ): 1.54-1.90 (2H, m) , 1.90-2.35 (2H, m), 2.76 (3H, d, J=4.4Hz), 2.60-3.50 (6H, m), 3.50-3.95 (2H, m) , 4.25-5.00 (IH, m) , 6.95-7.10 (2H, m) , 7.35-7.60 (6H, m) , 11.10- 11 . 40 ( IH , m ) 438 (CDC1 3 ): 1.30-2.13 (4H, m) , 2.27 (3H, s), 2.58-3.16 (7H, m) , 3.60 (IH, quinit, J=9.IHz) , 3.69-4.05 (IH, m) , 4.51-5.00 (IH, m) , 5.23 (2H, s), 7.05-7.25 (5H, m), 7.25-7.30 (IH, m), 7.30-7.46 (5H, m) , 7.92 (IH, d, J=8.IHz), 8.07 (IH, s), 8.83 (IH, s) 439 (CDCI 3 ): 0.95-1.60 (3H, m) , 1.71-2.21 (2H, m), 2.71-3.39 (7H, m) , 3.58-4.02 (IH, m) , 3.87 (IH, quint, J=6.6Hz), 4.38-4.82 (IH, m) , 7.22- 7.56 (6H, m), 7.99-8.13 (2H, m) 440 (CDCI 3 ): 1.25-1.77 (3H, ) , 1.77-1.99 (IH, ) , 2.35 (3H, ε), 2.44-3.15 (7H, m) , 3.42-3.65 (IH, m), 3.70 (3H, ε), 3.88 (2H, brε), 4.65- 4.89 (IH, m), 6.10-6.30 (2H, m) , 6.70-6.90 (IH, m), 7.10-7.38 (5H, m) 441 (CDCI 3 ): 1.29-2.00 (4H, m) , 2.35 (3H, ε), 2.51-2.51 (6H, m), 2.90-3.19 (IH, m) , 3.50- 3.80 (IH, m), 4.00 (2H, brε), 4.58-4.86 (IH, m), 6.22-6.48 (2H, m), 6.98-7.38 (6H, m) 442 (CDCI 3 ): 1.35-2.00 (4H, m) , 2.33 (3H, ε), 2.38 (3H, ε), 2.60-3.20 (7H, r), 3.65-4.05 (IH, m) , 4.50-5.00 (IH, m), 7.10-7.37 (7H, ) , 7.46 (2H, d, J=8.4Hz), 7.53-7.67 (4H, m) 443 (CDCI 3 ): 1.28-1/70 (2H, m) , 1.70-2.04 (2H, m) , 2.10 (3H, s), 2.32 (3H, s), 2.37 (3H, ε), 2.50-3.25 (7H, m) , 3.71-4.18 (IH, m) , 4.44- 4.92 (IH, m), 7.07-7.50 (12H, m) 444 (CDC1 3 ): 1.11-2.09 (4H, m) , 2.36 (3H, s), 2.53-3.08 (7H, m) , 3.63-4.02 (IH, m) , 3.83 (3H, ε), 4.43-4.91 (IH, m) , 5.10 (2H, s), 6.95 (2H, d, J=8.8Hz), 7.02-7.10 (2H, m) , 7.13-7.45 (10H, m), 7.53 (2H, d, J=8.8Hz) 445 (CDCI 3 ): 1.33-2.00 (4H, m) , 2.37 (3H, s), 2.60-3.25 (7H, m) , 3.60-4.20 (IH, m) , 4.45- 5.00 (IH, m), 5.21 (2H, s), 5.22 (2H, s), 7.01 (IH, d, J=8.3Hz), 7.11 (IH, dd, J=2.1Hz, 8.3Hz), 7.13-7.58 (20H, m) 446 (CDCI 3 ): 1.20-2.05 (4H, m) , 2.36 (3H, s), 2.40 (3H, s), 2.55-3.15 (7H, m) , 3.55-4.10 (IH, m) , 4.45-5.00 (IH, m), 5.10 (2H, s), 7.00-7.10 (2H, m), 7.05-7.44 (3H, m), 7.48 (2H, d, J=8.1Hz) 447 (CDCI 3 ): 1.20-2.05 (4H, m) , 2.36 (3H, s), 2.55-3.10 (7H, m) , 3.60-4.10 (IH, m) , 4.45- 4.90 (IH, m), 5.03 (2H, ε), 5.05 (2H, s), 5.19 (2H, s), 6.98 (IH, d, J=8.3Hz), 7.00-7.05 (2H, m), 7.08 (IH, dd, J=2.0Hz, 8.3Hz) , 7.15-7.55 (22H, m) 448 (CDCI 3 ): 1.35-1.70 (2H, m) , 1.70-2.02 , (2H, ) , 2.06 (6H, ε), 2.31 (3H, ε), 2.37 (3H, s), 2.55-3.26 (7H, m) , 3.65-4.18 (IH, m) , 4.44- 4.90 (IH, m), 7.02 (IH, d, J=2.5Hz), 7.08 (IH, dd, J=7.5Hz, 2.5Hz), 7.15-7.42 (9H, m) 449 (CDCI 3 ): 0.03-0.25 (0.8H, m) , 0.90-1.70 (3.2H, m), 2.00 (1.8H, s), 2.05-2.80 (7H, m) , 2.27 (1.2H, ε), 3.15-3.40 (IH, m) , 4.50-4.87 (IH, m), 4.99 (1.2H, s), 5.10 (0.8H, ε), 6.95-7.10 (2H, m), 7.10-7.57 (16H, m) 450 (CDC1 3 ): 1.30-2.05 (4H, m) , 2.33 (3H, s), 2.38 (3H, s), 2.60-3.30 (7H, m) , 3.60-4.05 (IH, m) , 4.50-4.95 (IH, m), 7.13-7.42 (9H, m), 7.48 (IH, d, J=7.8Hz), 7.64 (IH, dd, J=1.7Hz, 7.8Hz), 7.89 (IH, d, J=1.7Hz) 451 (CDC1 3 ): 1.30-2.10 (4H, m), 2.33 (3H, s), 2.41 (3H, s), 2.62-3.25 (3H, m), 2.90 (2H, t, J=6.0Hz), 3.72-4.20 (IH, m), 4.06 (2H, t, J=6.0Hz), 4.55-5.05 (IH, m) , 6.85-7.03 (3H, m), 7.13-7.40 (5H, ) , 7.47 (2H, d, J=8.4Hz), 7.55-7.68 (4H, m) 452 (CDCI 3 ): 1.42-1.71 (2H, m), 1.71-2.03 (2H, m), 2.37 (3H, s), 2.55-3.27 (7H, m) , 3.60-4.16 (IH, m), 3.82 (3H, s), 4.48-4.98 (IH, m), 5.10 (2H, s), 6.93-7.11 (4H, m), 7.15-7.56 (13H, m) 453 (CDCI 3 ): 1.36-2.03 (4H, m), 2.28 (3H, s), 2.37 (3H, s), 2.58-3.23 (7H, m) , 3.69-4.29 (IH, m), 4.45-5.00 (IH, m), 5.11 (2H, s), 7.03 (2H, d, J=8.8Hz), 7.14-7.57 (15H, m) 454 (CDCI 3 ): 1.29-2.01 (4H, m), 2.26 (3H, s), 2.32 (3H, s), 2.37 (3H, s), 2.59-2.89 (6H, m), 2.89-3.12 (IH, m) , 3.62-3.85 (IH, m) , 4.63- 4.87 (IH, m), 7.11-7.42 (9H, ), 7.44 (IH, dd, J=7.9Hz, 1.6Hz), 7.56 (2H, d, J=8.7Hz) 455 (CDCI 3 ): 1.32-1.55 (2H, m) , 1.55-2.05 (2H, m) , 2.36 (3H, s), 2.58-3.19 (7H, m) , 3.68-4.05 (IH, m), 4.58-4.98 (IH, m) , 5.11 (2H, ε), 7.05 (2H, d, J=8.8Hz), 7.15-7.68 (15H, m) 456 (CDC1 3 ): 1.20-2.04 (4H, m) , 2.35 (3H, ε), • 2.57-3.16 (7H, m) , 3.56-3.82 (IH, m) , 4.59- 4.89 (IH, ), 5.37 (2H, ε), 7.11-7.53 (12H, m), 8.11 (2H, d, J=8.5Hz) 457 (CDCI 3 ): 1.48-1.67 (2H, m) , 1.55 (3H, d, J=6.6Hz), 1.75-1.98 (2H, m) , 2.36 (3H, ε), 2.50-3.20 (8H, m) , 4.40-4.74 (2H, m) , 4.90 (IH, q, J=6.6Hz), 6.30 (IH, d, J=3.4Hz), 6.85 (IH, d, J=3.4Hz), 7.15-7.40 (5H, m) 458 (CDCI 3 ): 1.30-2.01 (4H, m) , 2.33 (3H, ε), 2.35 (3H, ε), 2.56-3.19 (8H, m), 2.62 (2H, t, J=7.8Hz), 2.96 (3H, ε), 3.44 (2H, t, J=7.8Hz), 3.62-4.18 (IH, m) , 4.43-5.02 (IH, m), 6.62-6.82 (3H, m), 7.11-7.35 (4H, m) , 7.45 (2H, d, J=8.4Hz), 7.53-7.68 (4H, m) 469 (DMSO-d 6 ): 1.24 (3H, t, J=7.2Hz) , 1.59-1.90 (2H, m), 1.90-2.37 (2H, m) , 2.75 (3H, d, J=4.4Hz), 2.65-3.47 (8H, m) , 3.47-3.82 (2H, m), 4.07-4.26 (2H, m) , 4.32-4.89 (IH, m), 7.15-7.44 (5H, m), 7.44-7.57 (2H, m) , 7.60- 7.79 (2H, m), 9.38-9.78 (2H, m) , 11.18-11.49 (IH, ) 468 (DMSO-d 6 ): 1.55-1.90 (2H, m) , 1.90-2.32 (2H, m), 2.00 (3H, ε), 2.16 (3H, s), 2.82 (3H, d, J=4.2Hz), 2.68-4.14 (6H, m) , 4.14-4.91 (3H, m), 6.70-6.98 (4H, m) , 7.23 (IH, d, J=8.6Hz), 7.38-7.50 (2H, m) , 7.50-7.60 (2H, m), 7.60-7.73 (2H, m) , 9.23 (IH, s), 9.66 (IH, s), 10.24-10.56 (IH, m) 467 (DMSO-d 6 ): 1.57-1.92 (2H, m) , 1.92-2.30 (2H, m), 2.56 (3H, s), 2.82 (3H, d, J=4.4Hz), 2.65-4.30 (6H, m) , 4.30-4.92 (3H, m), 6.80- 6.96 (2H, m), 7.00-7.19 (2H, m) , 7.40-7.52 (2H, m), 7.52-7.61 (2H, m) , 7.61-7.73 (2H, m) , 8.08 (IH, d, J=9.0Hz), 9.67 (IH, s), 10.50- 10.79 (IH, m) 472 (DMSO-d 6 ): 1.22-1.59 (IH, m) , 1.60-2.00 (3H, m), 2.00-2.41 (2H, m) , 2.62-3.31 (4H, m), 2.83 (3H, s), 3.56-4.06 (2H, m) , 4.31-4.92 (IH, m) , 7.09-7.42 (5H, m) , 7.42-7.79 (2H, m) , 7.89- 8.08 (2H, m), 8.23 (IH, s), 9.38 (IH, s), 11.27 (IH, brs) 471 (DMSO-d 6 ): 1.12 (3H, t, J=7.6Hz), 1.22-1.53 (IH, m), 1.53-1.97 (3H, m) , 1.97-2.45 (2H, m) , 2.13 (3H, s), 2.15 (3H, s), 2.34 (2H, q, J=7.6Hz), 2.60-3.30 (4H, m) , 2.83 (3H, s), 3.51-4.15 (2H, m) , 4.15-4.95 (IH, m) , 6.96- 7.47 (7H, m), 9.29 (IH, s), 11.24 (IH, brs) 474 (DMSO-d 6 ): 1.61-1.91 (2H, m) , 1.91-2.38 (2H, m), 2.00 (3H, s), 2.70-3.30 (2H, m) , 2.80 (3H, d, J=4.4Hz), 3.30-3.96 (4H, m) , 4.23-4.52 (2H, m), 4.52-4.88 (IH, m) , 6.93 (2H, d, J=9.0Hz), 7.51 (2H, d, J=9.0Hz), 7.61 (2H, d, J=9.0Hz), 7.95 (2H, d, J=9.0Hz), 8.28 (IH, s), 9.39 (IH, s), 9.94 (IH, s), 10.80-11.18 (IH, m) 475 (DMSO-d 6 ): 1.61-1.96 (2H, m) , 1.96-2.35 (2H, ), 2.68-3.34 (2H, m), 2.80 (3H, s), 3.34-4.12 (4H, m), 4.27-4.88 (3H, m) , 7.10 (2H, d, J=8.8Hz), 7.36 (2H, d, J=8.8Hz), 7.62 (2H, d, J=8.4Hz), 7.95 (2H, d, J=8.4Hz), 8.28 (IH, s), 9.40 (IH, s), 10.36 (3H, brs), 11.16 (IH, brs) 461 (DMSO-d 6 ): 1.51-1.92 (2H, m) , 1.95-2.30 (2H, m), 2.73 (3H, d, J=4.2Hz) , 2.61-3.74 (7H, m) , 3.74-4.96 (2H, m) , 6.21-6.52 (4H, m) , 7.09 (IH, d, J=8.4Hz), 7.38 (2H, d, J=8.2Hz), 7.50- 7.69 (3H, m), 9.43 (IH, s), 9.54 (IH, s), 10.87-11.18 (IH, m) 478 (CDC1 3 ): 1.37-1.72 (2H, m) , 1.72-2.10 (2H, m) , 2.33 (3H, s), 2.41 (3H, s), 2.62 (3H, s), 2.62-3.30 (3H, m) , 2.91 (2H, t, J=6.0Hz), 3.65-4.30 (IH, m) , 4.10 (2H, t, J=6.0Hz), 4.48-5.10 (IH, m), 6.70-6.88 (2H, m) , 7.11- 7.28 (2H, m), 7.42-7.55 (2H, m) , 7.55-7.69 (4H, ), 8.01-8.17 (IH, m) 479 (CDCI 3 ): 1.25-1.71 (2H, m) , 1.71-2.21 (2H, m) , 2.34 (3H, ε), 2.42 (3H, s), 2.59-3.22 (3H, m) , 2.93 (2H, t, J=5.6Hz), 3.67-4.25 (IH, m) , 4.13 (2H, t, J=5.6Hz), 4.50-5.04 (IH, ) , 6.86-7.06 (2H, m), 7.11-7.28 (2H, m) , 7.35-7.75 (6H, m) , 8.10-8.30 (2H, m) 480 (CDCI 3 ): 1.30-2.09 (4H, m) , 2.18 (3H, s), 2.22 (3H, s), 2.34 (3H, s), 2.40 (3H, s), 2.62-3.23 (3H, m), 2.88 (2H, t, J=6.0Hz), 3.70-4.19 (IH, m), 4.03 (2H, t, J=6.0Hz), 4.52-5.06 (IH, m) , 6.65-6.82 (2H, m), 6.88 (IH, s), 7.14-7.25 • (2H, ), 7.40-7.55 (3H, m), 7.55-7.70 (4H, m) 481 (CDC1 3 ): 1.31-1.71 (2H, m) , 1.71-2.07 (2H, m), 2.13 (3H, s), 2.34 (3H, ε), 2.40 (3H, ε), 2.56-3.26 (3H, m) , 2.88 (2H, t, J=6.0Hz), 3.65-4.29 (IH, m) , 4.03 (2H, t, J=6.0Hz), 4.50-5.07 (IH, m), 6.78-6.95 (2H, m), 7.14- 7.25 (2H, m), 7.26 (IH, s), 7.33-7.45 (2H, m), 7.45-7.55 (2H, m), 7.55-7.69 (4H, m) 482 (250 MHz: CDC1 3 ): 1.32-2.01 (4H, m) , 2.10 (3H, s), 2.32 (3H, s), 2.34 (3H, s), 2.56-3.21 (7H, m), 3.69-4.05 (IH, m), 4.55-4.95 (lH,m), 6.03 (IH, d, J=3.1Hz), 6.29 (IH, dd, J=1.9Hz, 3.1Hz), 6.99 (IH, d, J=2.3Hz), 7.09 (IH, dd, J=2.3Hz, 8.5Hz), 7.31 (IH, d, J=1.9Hz), 7.34- 7.50 (5H, m) 484 (CDC1 3 ): 1.40-1.72 (2H, ) , 1.72-2.11 (2H, m), 2.28 (3H, s), 2.34 (3H, s), 2.40 (3H, s), 2.63-3.24 (3H, m) , 2.89 (2H, t, J=5.5Hz), 3.76-4.12 (IH, m) , 4.03 (2H, t, J=5.5Hz), 6.79 (2H, d, J=8.6Hz), 7.07 (2H, d, J=8.6Hz),7.18 (2H, d, J=8.5Hz), 7.47 (2H, d, J=8.2Hz), 7.55- 7.69 (4H, m) 485 (DMSO-d 6 ): 1.09 (3H, t, J=7.OHz) , 1.50-1.85 (2H, m), 1.85-2.35 (2H, m) , 2.58-2.91 (IH, m) , 2.75 (3H, d, J=4.6Hz), 2.91-3.47 (7H, m) , 3.47-3.84 (2H, ) , 4.32-4.83 (IH, m) , 5.60- 7.09 (2H, ), 6.50 (IH, dd, J=8.0Hz, 1.5Hz), 6.68 (IH, d, J=1.5Hz), 7.17-7.46 (5H, ), 7.51 (IH, d, J=8.0Hz), 8.31 (IH, t, J=5.5Hz ) , 10.92-11.20 (IH, m) Example 488 1.50 g of 7-chloro-3-methylthio-4-{4-[N- methy1-N-(2-phenylethyl)amino]-1-piperidinylcarbony1}- oxindole was added to a suεpenεion of 15 g of Raney nickel in 30 ml of methanol. The mixture waε εtirred at room temperature for 1 hour. The Raney nickel waε εeparated by decantation and washed with methanol. The decanted solution and the washingε were combined and concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (eluant: methylene chloride/methanol = 30/1). The product was converted into a hydrochloride in ethanol to obtain 0.63 g of 7-chloro-4-{4-[N-methyl-N-(2-phenylethyl)amino]-l- piperidinylcarbonyl}oxindole hydrochloride as a colorlesε amorphouε. -NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.45-1.82 (2H, m) , 1.82-2.30 (2H, m) , 2.76 (3H, d, J=4.5 Hz), 2.91- 3.75 (8H, m), 3.52 (2H, s), 4.30-4.85 (IH, m) , 6.94 (IH, d, J=8.5 Hz), 7.15-7.50 (6H, m) , 10.55-10.79 (IH, m), 10.95 (IH, s) Example 489 0.88 ml of triethylamine, 0.1 g of 10% palladium carbon were added to 20 ml of a εolution of 0.86 g of 7-chloro-4-{4-[N-methyl-N-(2-phenylethyl)- amino]-l-piperidinylcarbonyl}oxindole in ethanol. The mixture was subjected to hydrogenation at normal pres¬ sure at room temperature for 6 hours. The catalyst was removed by filtration. The filtrate was subjected to diεtillation to remove the εolvent. The reεidue waε dissolved in methylene chloride. The solution was water-washed, dried with anhydrouε magneεium sulfate, and concentrated under reduced preεεure. The reεidue waε purified by a silica gel column chromatography (eluant: methylene chloride/methanol =30/1). The product was converted into a hydrochloride in ethanol to obtain 0.19 g of 4-{4-[N-methyl-N-(2-phenylethyl)amino]- l-piperidinylcarbonyl}oxindole hydrochloride as a colorleεε amorphous. Η-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.44-1.85 (2H, m) , 1.85-2.34 (2H, ) , 2.76 (3H, d, J=4.5 Hz), 2.93- 3.84 (10H, m), 4.30-4.87 (IH, m) , 6.78-7.00 (2H, m), 7.11-7.49 (6H, ) , 10.55 (IH, s), 10.78-11.06 (IH, m) Example 490 0.20 g of 10% palladium carbon was added to a solution of 1.91 g of 4-[N-methyl-N-(2-phenylethyl)- amino]-1-[4-(4-methylphenyl)-3-benzyloxybenzoyl]- piperidine in 40 ml of ethanol. The mixture was stirred at a hydrogen gas presεure of 1 atm. at room temperature for 2 hours. The catalyst was collected by filtration and washed with ethanol. The filtrate and the washingε were combined and concentrated under reduced preεεure. The reεidue waε diεεolved in ethanol. The εolution waε mixed with an equimolar amount of 5 N hydrochloric acid. The mixture was concentrated under reduced presεure. The reεidue waε crystallized from ethanol and then recrystallized from ethanol-water to obtain 1.22 g of 4- [N-methyl-N-(2-phenylethyl)amino]-1-[4-(4-methylphenyl)- 3-hydroxybenzoyl]piperidine hydrochloride as a white . powder. Melting point: 218-221°C Using suitable starting materials and in the same manner as in Example 490, there were obtained the compounds of the above-mentioned Examples of 157, 316, 359, 362-363, 368-372, 374-378, 381-383, 385, 390, 393, 397, 401, 434, 436 and 461-468. Example 491 3.94 ml of a 2 M aqueouε potaεεium carbonate εolution and 2 ml of water were added to a εolution of 1.35 g of 4-[N-methyl-N-(2-phenylethyl)amino]-l-[4-(4- acetyloxyphenyl)-3-acetyloxybenzoyl]piperidine in 13 ml of methanol. The mixture was stirred for 30 minutes. Water was added thereto. The mixture was extracted with dichloromethane. The extract was washed with water and a saturated aqueous sodium chloride solution, dried with magnesium εulfate, and subjected to distillation to remove the solvent. The residue was purified by a silica gel column chromatography (eluant: dichloro- methane/methanol = 30/1 to 20/1). The product waε converted to a hydrochloride with an equimolar amount of 5 N hydrochloric acid, in ethanol-water. The hydro¬ chloride was recrystallized from ethanol to obtain 0.41 g of 4-[N-methyl-N-(2-phenylethyl)amino]-l-[4-(4- hydroxyphenyl)-3-hydroxybenzoyl]piperidine hydrochloride as a white powder. Melting point: 218-223°C Η-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.55-1.90 (2H, m) , 1.94-2.30 (2H, m) , 2.60-3.50 (6H, m) , 2.78 (3H, d, J=4.4 Hz), 3.50-3.73 (IH, m) , 3.73-4.83 (2H, m) , 6.80 (2H, d, J=8.6 Hz), 6.87 (IH, d, J=7.6 Hz), 6.98 (IH, s), 7.19-7.48 (8H, m) , 9.48 (IH, ε), 9.79 (IH, ε), 10.81-11.10 (IH, m) Uεing suitable starting materials and in the same manner as in Example 491, there were obtained the compounds of the above-mentioned Examples of 157, 316, 359, 362-363, 368-372, 374-378, 381-383, 385, 390, 393, 397, 401, 434, 436 and 461-468. Example 492 1 ml of methanol was dropwise added, at about 80°C, to a mixture of 1.0 g of 4-[N-methyl-N-(2- phenylethyl)amino]-1-(2-methoxycarbonylpyridin-5- yl)carbonylpiperidine, 0.12 g of sodium borohydride and 3.88 g of tert-butanol. (This gave rise to foaming.) In this state, the mixture was refluxed by heating, for 1.5 hours. The reaction mixture was returned to room temperature and mixed with 1 ml of water and 1 ml of acetic acid. The mixture was stirred for 5 minutes and then subjected to distillation to remove the solvent. The residue was mixed with water for dissolution. The εolution waε made baεic with an aqueous sodium hydroxide solution and then extracted with chloroform. The extract waε washed with water and a saturated aqueous sodium chloride solution, dried with magnesium sulfate, and subjected to distillation to remove the solvent. The resiude waε purified by a silica gel column chromatography (eluant: dichloromethane/methanol = 45/1 to 25/1). The product was converted to a hydrochloride with 2 equivalents of 5 N hydrochloric acid, in ethanol. The hydrochloride was crystallized from ethyl acetate- ethanol and recrystallized from ethanol-water to obtain 0.32 g of 4-[N-methyl-N-(2-phenylethyl)amino]-l-(2- hydroxymethylpyridin-5-yl)carbonylpiperidine dihydro¬ chloride as colorlesε priεm-like cryεtals. Melting point: 219-221°C (decompd.) Example 493 A solution of 56 mg of sodium nitrite in 1 ml of water was dropwise added, with ice-cooling, to a suspension of 0.40 g of 4-[N-methyl-N-(2-phenylethyl)- amino]-1-[4-(4-hydroxypheny1)-3-aminobenzoyl]piperidine in 4 ml of water. Separately, a εolution of 0.13 g of sodium cyanide in 4 ml of water was added to a εuspen- sion of 0.11 g of copper chloride in 4 ml of water to prepare an aqueous copper cyanide solution. 8 ml of toluene was added to the copper cyanide solution. To the mixture was added the above aqueous diazonium salt solution. The mixture was stirred at room temperature for 2 hourε. Ice waε added thereto and the resulting mixture was made basic with a 25% aqueous sodium hydroxide solution. The mixture waε extracted with ethyl acetate. The extract was washed with water and a saturated aqueous sodium chloride solution in this order, dried with sodium sulfate, and concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (eluant: methylene chloride/ methanol = 50/1 to 20/1) and then by a thin-layer chromatography (developer: methylene chloride/methanol = 9/1). The product was converted into a hydrochloirde. The hydrochloride was crystallized from ethanol and then recrystallized from ethanol-water to obtain 52 mg of 4- [N-methyl-N-(2-phenylethyl)amino]-1-[4-(4-hydrox- yphenyl)-3-cyanobenzoyl]piperidine hydrochloride as a white powder. Melting point: 258-260°C Using suitable starting materials and in the same manner as in Example 493, the compounds of the above-mentioned Exampleε 277, 292 and 293 were obtained. Example 494 100 ml of a 40% εolution of methyla ine in methanol was added to 30 ml of a solution of 1.50 g of 4-[N-methyl-N-(2-phenylethyl)amino]-1-(4-methoxy- carbonylbenzoyl)piperidine in methanol. The mixture waε allowed to stand at 100°C for 90 minutes in a sealed tube. The reaction mixture waε cooled and concentrated under reduced preεεure. The residue was purified by a εilica gel column chromatography (eluant: methylene chloride/methanol = 30/1). The product waε converted into a hydrochloride in ethanol. The hydrochloride was recrystallized from ethanol-ethyl acetate to obtain 0.92 g of 4-[N-methyl-N-(2-phenylethyl)amino]-l-(4-methyl- aminocarbonylbenzoyl)piperidine hydrochloride aε a white powder. Melting point: 242-245°C Example 495 3.1 g of εodium cyanide waε added, with ice- cooling and εtirring, to a solution of 3.3 g of 4-[N- metyl-N-(2-phenylethyl)amino]piperidine in 200 ml of isopropyl alcohol. The mixture was stirred at room temperature for 5 minutes. Thereto were added 2.0 g of 5-nitrothiophene-2-carboxyaldehyde and 22.1 g of manganese dioxide. The mixture waε εtirred for 30 minuteε with ice-cooling. Thereto waε added methylene chloride. The reεulting inεolubles were collected by filtration through Celite and washed with methylene chloride. The filtrate and the washingε were combined and concentrated under reduced preεεure. To the reεidue was added 300 ml of ethyl acetate. The mixture was washed with water (100 ml x 2) and a saturated aqueous sodium chloride εolution in thiε order, dried with sodium sulfate, and concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (eluant: methylene chloride/methanol = 30/1). The product was converted into a hydrochloride. The hydrochloride was crystallized from ethanol and recrystallized from ethanol-water to obtain 3.1 g of 4- [N-metyl-N-(2-phenylethyl)amino]-1-(5-nitrothiophen-2- yl)carbonylpiperidine hydrochloride aε a light yellow powder. Melting point: 230-234°C (decompd.) Uεing suitable starting materials and in the same manner as in Example 495, there were obtained the compoundε of the above-mentioned Exampleε 1, 3-47, 49- 257, 277-421 and 423-475. Example 496 1.10 g of 4-[N-metyl-N-(2-phenylethyl)amino]- 1-(5-nitrothiophen-2-yl)carbonylpiperidine hydrochloride waε converted into a free form and diεεolved in 25 ml of ethyl acetate. Thereto were added 0.70 ml of propionic anhydride and 0.10 g of 10% palladium carbon. The mixture waε εtirred at a hydrogen preεεure of 1 atm. at room temperature for 2 hourε. 0.10 g of 10% palladium carbon waε added, and the mixture waε εtirred overnight at room temperature. 0.10 g of 10% palladium carbon waε added, and the mixture was stirred at room temperature for 8 hours. The catalyεt was collected by filtration and washed with ethyl acetate. The filtrate and the washings were combined. The mixture was washed with a diluted aqueous sodium hydroxide solution and a satu¬ rated aqueous sodium chloride solution in this order, dried with sodium sulfate, treated with active carbon, and concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (eluant: methylene chloride/methanol = 30/1 to 20/1) and then by a thin-layer chromatography (developer: methylene chloride/methanol = 9/1). The product was converted into a hydrochloride. The hydrochloride was dried under reduced preεεure to obtain 0.11 g of 4-[N- metyl-N-(2-phenylethyl)amino]-1-(5-propionylamino- thiophen-2-yl)carbonylpiperidine hydrochloride aε a light brown amorphouε. Η-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.09 (3H, t, J=7.4 Hz), 1.55-1.90 (2H, m) , 2.20-2.25 (2H, m) , 2.38 (2H, q, J=7.4 Hz), 2.78 (3H, d, J=4.4 Hz), 2.97- 3.52 (6H, m), 3.52-3.75 (IH, m), 4.33-4.55 (2H, m), 6.60 (IH, d, J=4.0 Hz), 7.21 (IH, d, J=4.0 Hz), 7.26-7.45 (5H, m) , 10.45-10.65 (IH, m) , 11.46 (IH, s) Example 497 A solution of 1.5 g of 4-[N-methyl-N-(2- phenylethyl)amino]piperidine in 15 ml of dimethyl- formamide was refluxed for 24 hours, then treated with water, and extracted with ethyl acetate. The exract waε waεhed with water and a εaturated aqueous sodium chloride solution, dried with magneisum sulfate, and • subjected to distillation to remove the solvent. The residue was purified by a silica gel column chromato¬ graphy (eluant: dichloromethane/methanol = 30/1). The product was converted into a hydrochloride with an equivalent of 5 N hydrochloric acid in ethanol. The hydrochloride was recrystallized from ethyl acetate- ethanol to obtain 0.26 g of 4-[N-methyl-N-(2-phenyl¬ ethyl)amino]-l-formylpiperidine hydrochloride aε a white powder. Melting point: 180-182°C Example 498 0.3 ml of hydrazine hydrate waε added to a εolution of 0.57 g of 4-[N-methyl-N-(2-phthalimido- ethyl)amino]-l-[4-(l,2,4-triazol-1-yl)benzoyl]piperidine in 5 ml of ethanol. The mixutre waε refluxed for 5 minutes. 5 ml of ethanol was added, and the mixture waε refluxed for 5 minuteε. The reaction mixture was returned to room temperature and treated with a satu¬ rated aqueous sodium hydrogencarbonate solution and then extracted with chloroform. The extract waε waεhed with a saturated aqueous εodium chloride εolution, dried with anhydrouε magneεium εulfate, and εubjected to diεtilla- tion to remove the εolvent. The residue was purified by thin-layer silica gel column chromatography (developer: methylene chloride/methanol/ammonia water = 50/10/1). The product was converted into a hydrochloride with an equimolar amount of 5 N hydrochloric acid in ethanol- to obtain 0.06 g of 4-[N-methyl-N-(2-aminoethyl)amino]-l- [4-(1,2,4-triazol-l-yl)benzoyl]piperidine dihydrochlo¬ ride aε a yelolow amorphouε. Η-NMR (200 MHz, DMSO-d 6 ) δ ppm: 1.47-1.86 (2H, m), 1.86-2.30 (2H, m) , 2.41-4.03 (8H, m) , 2.69 (3H, ε), 4.30-4.90 (IH, m) , 7.60 (2H, d, J=8.5 Hz), 7.94 (2H, d, J=8.5 Hz), 7.72-9.75 (4H, m) , 8.26 (IH, ε), 9.39 (IH, ε) 26 - 450 - Pharmacological Test Materials and method used in the test: A sample for perfuεing blood in femoral artery under a constant pressure was prepared as follows. Adult male or female mongrel dogs each weigh¬ ing about 15-30 kg were anesthetized with pentobarbital sodium (30 mg/kg i.v.). Heparin sodium (700 U/kg) was administered to them intravenously. Then, the arterial blood of each dog was perfused from the carotid to the right femoral artery using a reciprocating pump at a rate of 90 ml/min. The blood, which had pasεed in parallel to the perfuεion circuit, waε returned to the εample from the left femoral vein. During the teεt, a tracheal cannula was fitted to practise artificial respiration using an artificial respirator (a product of Shinano Seiεakuεho), and pento¬ barbital sodium (4 mg/kg/hr) and heparin sodium (100 U/kg/hr) were continuously adminiεtered intravenouεly to maintain aneεthesia and the anti-coagulation activity of blood. The amount of blood flow in femoral artery was measured in the perfusion circuit by the use of an electromagnetic blood flow meter (FV-2100 manufactured by Nihon Koden) and reported on a thermal-pen type recorder (RECTI-HORIZ 8K manufactured by Nihon Koden Sanei) . Each of the teεt compoundε εhown below was dissolved in a solvent (purified water, hydrochloric acid, N,N-dimethylformamide) in a concentration of 10 μM/ml. The solution was diluted as necessary and a volume of 10-30 μl was administered into the femoral artery of each dog. In the test results, the amount of blood flow of teεt compound-adminiεtered group minuε the amount of blood flow of control group (solvent alone-administered group) was reported as change in blood flow amount (ml/min). The compounds of the present invention other than those shown below gave the same effects. Test compounds 1. 5-{4-[ -methyl-N-(2-phenylethyl)amino]-1- piperidinylcarbonyl}-2-oxindole hydrochloride 2. 4-[N-methyl-N-(2-ρhenylethyl)amino]-l-(4- • nitrobenzoyl)piperidine fumarate 3. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(4- phenylureidobenzoyl)piperidine 4. 4-[N-methyl-N-(2-phenylethyl)amino]-l-(4- methylureidobenzoyl)piperidine hydrochloride 5. 4-[N-methyl-N-(2-phenylethyl)amino]-l-(4- propionylaminobenzoyl)piperidine 1/2 fumarate 6. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[4-(1- imidazolyl)benzoyl]piperidiene hydrochloride 7. 4-[N-methyl-N-(2-phenylethyl)amino]-l-(4- allylureidobenzoyl)piperidine hydrochloride 8. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(4- phenylthioureidobenzoyl)piperidine 9. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(3,4- dimethoxybenzoyl)piperidine oxalate 10. 5-{4-[N-methyl-N-(2-phenylethyl)amino]-l- piperidinylcarbonyl}-2,3-dihydro-2-oxobenzimidazole hydrochloride 11. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(3- nitrobenzoyl)piperidine fumarate 12. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(3- methylureidobenzoyl)piperidine hydrochloride 13. 4-[N-methyl-N-(2-phenylethyl)amino]-l-[4-(2- oxo-1-pyrrolidinyl)benzoyl]piperidine oxalate 14. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(3- propionylaminobenzoyl)piperidine hydrochloride 15. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[3-(2- oxo-1-piperidinyl)benzoyl]piperidine hydrochloride 16. 4-[N-methyl-N-(2-phenylethyl)amino]-l-(4- fluorobenzoyl)piperidine oxalate 17. 4-[N-methyl-N-(2-phenylethyl)amino]-l- anilinothiocarbonylpiperidine 18. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(4- iεopropylureidobenzoyl)piperidine hydrochloride 19. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(4-t- butylureidobenzoyl)piperidine hydrochloride 20. 4-[N-methyl-N-(2-phenylethyl)amino]-1- anilinocarbonylpiperidine 21. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[4-(3- methyl-l-pyrazolyl)benzoyl]piperidine hydrochloride 22. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[4-(2- oxo-l-imidazolidinyl)benzoyl]piperidine 23. 4-[N-methyl-N-(2-phenylethyl)amino]-l-[4- (2(IH)-imidazolyl)benzoyl]piperidine trihydrochloride 24. 4-[N-methyl-N-(2-phenylethyl)amino]-l-[4- (2(IH)-benzoimidazolyl)benzoyl]piperidine 25. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[4-(2- pyridyl)benzoyl]piperidine dihydrochloride 26. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(4- methylaminobenzoyl)piperidine dihydrochloride 27. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[4- (1,2,4-triazol-l-yl)benzoyl]piperidine 28. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(4- dimethylaminobenzoyl)piperidine hydrochloride 29. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[4-(1- pyrrolyl)benzoyl]piperidine hydrochloride 30. 4-[ -methyl-N-(2-phenylethyl)amino]-1-(3- methoxy-4-nitrobenzoyl)piperidine oxalate 31. 4-[N-methyl-N-(2-phenylethyl)amino]-l-(3- methoxy-4-methylureidobenzoyl)piperidine hydrochloride 32. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[4-(3,3- dimethyl-l-methylureido)benzoyl]piperidine hydrochloride 33. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(4- acetylbenzoyl)piperidine hydrochloride 34. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(4- dimethylaminocarbonylbenzoyl)piperidine 35. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[4-(2- oxazolin-2-yl)benzoyl]piperidine 36. 4-[N-methyl-N-(2-phenylethyl)amino]-l- dimethylaminocarbonylpiperidine hydrochloride 37. 4-[N-methyl-N-(2-phenylethyl)amino]-1- methylaminocarbonylpiperidine hydrochloride 38. 4-[N-methyl-N-(2-phenylethyl)amino]-1- ethoxycarbonylpiperidine hydrochloride 39. 4-[N-methyl-N-(2-phenylethyl)amino]-l- acetylpiperidine hydrochloride 40. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(4- nitro-3-methylbenzoyl)piperidine hydrochloride 41. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(4- methylamino-3-methylbenzoyl)piperidine hydrochloride 42. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(3,5- dimethyl-4-propionylaminobenzoyl)piperidine hydrochloride 43. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(3,5- dimethyl-4-methylureidobenzoyl)piperidine hydrochloride 44. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(3,5- dimethyl-4-aminobenzoyl)piperidine oxalate 45. 4-[N-methyl-N-(2-phenylethyl)amino]-l-(3- methyl-4-amino-5-methoxybenzoyl)piperidine oxalate 46. 4-[N-methyl-N-(2-phenylethyl)amino]-l-(3- methyl-4-methylureido-5-methoxybenzoyl)piperidine oxalate 47. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(2- chloro-4-nitrobenzoyl)piperidine hydrochloride 48. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(2- methyl-4-nitrobenzoyl)piperidine hydrochloride 49. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(2- fluoro-4-nitrobenzoyl)piperidine hydrochloride 50. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[4- (1,2,4-triazol-4-yl)benzoyl]piperidine dihydrochloride 51. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[4- (1,2,3,4-tetrazol-l-yl) enzoyl]piperidine 52. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(2- methyl-4-propionylaminobenzoyl]piperidine hydrochloride 53. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(2- chloro-4-propionylaminobenzoyl]piperidine hydrochloride 54. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[3- methyl-4-(1,2,4-triazol-1-yl)benzoyl]piperidine 55. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[3- nitro-4-(1,2,4-triazol-l-yl)benzoyl]piperidine 56. 4-{N-methyl-N-[2-(2-pyridyl)ethyl]amino}-l-[4- (1,2,4-triazol-l-yl)benzoyl]piperidine dihydrochloride 57. 4-[N-methyl-N-(2-phenylethyl)amino]-l-[3- hydroxyamino-4-(1,2,4-triazol-1-yl)benzoyl]piperidine 58. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[3- methoxy-4-(1,2,4-triazol-l-yl)benzoyl]piperidine hydrochloride 59. 4-[N-methyl-N-(2-phenylethyl) mino]-l-[3- hydroxy-4-(1,2,4-triazol-l-yl)benzoyl]piperidine hydrochloride 60. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[2-(- 1,2,4-triazol-l-yl)acetyl]piperidine dihydrochloride 61. 4-[N-methyl-N-(3-phenylpropyl)amino]-1-[4-(- 1,2,4-triazol-l-yl)benzoyl]piperidine hydrochloride 62. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(6- chloro-3-pyridyl)carbonylpiperidine hydrochloride 63. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[6- (1,2,4-triazol-l-yl)-3-pyridyl]carbonylpiperidine 64. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[4-(1- pyrrolidinyl)benzoyl]piperidine oxalate 65. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[4- (1,2,4-triazol-l-yl)-3-cyanobenzoyl]piperidine hydrochloride 66. 4-(N-methyl-N-benzylamino)-1-[4-(1,2,4-tri- azol-1-yl)benzoyl]piperidine 67. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[3- carbamoyl-4-(1,2,4-triazol-l-yl)benzoyl]piperidine 68. 4-[N-methyl-N-(2-phenylethyl)amino]-l-[3- (1,2,4-triazol-l-yl)benzoyl]piperidine hydrochloride 69. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[2- ' (1,2,4-triazol-l-yl)benzoyl]piperidine hydrochloride 70. 4-[ -methyl-N-(2-phenylethyl)amino]-l-[4- (1,2,4-triazol-l-yl)methylbenzoyl]piperidine hydrochloride 71. 4-{N-methyl-N-[2-(4-methoxypheny1)ethyl]- amino}-l-[4-(1,2,4-triazol-l-yl)benzoyl]piperidine 72. 4-{N-methyl-N-[2-(3-nitrophenyl)ethyl] mino}- 1-[4-(1,2,4-triazol-l-yl)benzoyl]piperidine 73. 4-(N-ethyl-N-benzylamino]-1-[4-(1,2,4-triazol- 1-yl)benzoyl]piperidine hydrochloride 74. 4-{N-methyl-N-[2-(6-methyl-2-pyridyl)ethyl]- amino>-1-[4-(1,2,4-triazol-l-yl)benzoyl]piperidine trihydrochloride 75. 4-{N-methyl-N-[2-(4-chlorophenyl)ethyl]amino}- 1-[4-(1,2,4-triazol-l-yl)benzoyl]piperidine 76. 4-{N-methyl-N-[2-(3-aminophenyl)ethyl]amino}- 1-[4-(1,2,4-triazol-l-yl)benzoyl]piperidine 77. 4-[N-methyl-N-(2-phenylethyl)amino]-l-[3- (1,2,4-triazol-l-yl)-4-aminobenzoyl]piperidine hydrochloride 78. 4-[N-methyl-N-(2-phenoxyethyl) mino]-1-[4- (1,2,4-triazol-l-yl)benzoyl]piperidine dihydrochloride 79. 4-{N-methyl-N-[2-(3,4-dimethoxyphenyl)ethyl]- amino}-!-[4-(1,2,4-triazol-l-yl)benzoyl]piperidine hydrochloride 80. 4-[N-(2-hydroxyethyl)-N-(2-phenylethyl)amino]- 1-[4-(1,2,4-triazol-l-yl)benzoyl]piperidine 81. 4-{N-methyl-N-[2-(3-methylureidophenyl)- ethyl]amino}-1-[4-(1,2,4-triazol-l-yl)benzoyl]piperidine 82. 4-{N-methyl-N-[2-(3-acetylaminophenyl)ethyl]- amino}-l-[4-(l,2,4-triazol-l-yl)benzoyl]piperidine 83. 4-[N-methyl-N-(2-phenylethyl)amino]-l-[4- (1,2,4-triazol-l-yl)-3-ethylthioureidobenzoyl]piperidine 84. 4-{N-methyl-N-[2-(3-hydroxypheny1)ethyl]- amino}-l-[4-(1,2,4-triazol-l-yl)benzoyl]piperidine 85. 4-[ -methyl-N-(2-phenylethyl)amino]-1-[2- methylureido-5-(1,2,4-triazol-l-yl)benzoyl]piperidine 86. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(3,5- dimethyl-4-acrylaminobenzoyl)piperidine hydrochloride 87. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[4- (1,2,4-triazol-l-yl)-3-(2-dimethylaminoethoxy)- benzoyl]piperidine 88. 4-[N-methyl-N-(4-chlorophenyl)methylamino]-l- [4-(1,2,4-triazol-l-yl)benzoyl]piperidine 89. 4-(6-Methoxy-l,2,3,4-tetrahydroisoquinolin-2- yl)-1-[4-(1,2,4-triazol-l-yl)benzoyl]piperidine 90. 4-(6-Hydroxy-l,2,3,4-tetrahydroisoquinolin-2- yl)-1-[4-(1,2,4-triazol-l-yl)benzoyl]piperidine 91. 4-[N-methyl-N-{2-[2-(2-dimethylaminoethoxy)- phenyl]ethyl}amino]-l-[4-(l,2,4-triazol-l-yl)benzoyl]- piperidine dihydrochloride 92. 4-{N-methyl-N-[2-(2-pyridyl)ethyl]amino}-!- benzoylpiperidine dihydrochloride 93. 4-{N-methyl-N-[2-(2-pyridyl)ethyl]amino}-l- (3,4,-dimethoxybenzoyl)piperidine dihydrochloride 94. 4-{N-methyl-N-[2-( -methylthiophenyl)ethyl]- amino}-l-[4-(1,2,4-triazol-l-yl)benzoyl]piperidine 95. 4-{N-methyl-N-[2-(4-aminophenyl)ethyl]amino}- 1-(3,4,-dimethoxybenzoyl)piperidine hydrochloride 96. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[2- (1,2,4-triazol-l-yl)-5-hydroxymethylbenzoyl]piperidine hydrochloride 97. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[3-(2- ethoxycarbonylvinyl)benzoyl]piperidine hydrochloride 98. 4-{N-methyl-N-[2-(4-hydroxypheny1)ethyl]- amino}-l-[4-(1,2,4-triazol-4-yl)benzoyl]piperidine 99. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[4- acetylamino-3-(1,2,4-triazol-4-yl)benzoyl]piperidine hydrochloride 100. 4-[N-methyl-N-(2-phenylethyl)amino]-l-(3- methyl-4-propionylamino-5-vinylbenzoyl)piperidine hydrochloride 101. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[3,4- di(1,2,4-triazol-l-yl)benzoyl]piperidine hydrochloride 102. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(2,5- dimethyl-4-propionylaminobenzoyl)piperidine hydrochloride 103. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(3,5- dichloro-4-aminobenzoyl)piperidine 104. 4-[ -methyl-N-(2-phenylethyl)amino]-1-(3- methyl-4-propionylamino-5-aminobenzoyl)piperidine hydrochloride 105. 4-[N-methyl-N-(2-phenylethyl)amino]-l-(3- pyridyl)carbonylpiperidine dihydrochloride 106. 4-[N-methyl-N-(2-phenylethyl)amino]-l-(4- propionylamino-2-methoxybenzoyl)piperidine hydrochloride 107. 4-[N-methyl-N-(2-phenylethyl) mino]-1-(3- methyl-4-propionylamino-5-hydroxymethylbenzoyl)- piperidine oxalate 108. 4-[N-methyl-N-(2-phenylethyl)amino]-l-(6- amino-3-pyridyl)carbonylpiperidine dihydrochloride 109. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[6-(1- pyrrolyl)-3-pyridyl]carbonylpiperidine 110. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(6- propionylamino-3-pyridyl)carbonylpiperidine hydrochloride 111. 4-Methyl-6-{4-[N-methyl-N-(2-phenylethyl)- amino]-1-piperidinylcarbonyl}-1,2,3-benzotriazole hydrochloride 112. 4-(4-Phenyl-l-piperidinyl)-l-acetylpiperidine 113. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(2,2,2- trifluoroacetyl)piperidine hydrochloride 114. 4-[N-methyl-N-(2-phenylethyl)amino]-!-(4- amino-3-nitrobenzoyl)piperidine hydrochloride 115. 2-Ethyl-5-{4-[N-methyl-N-(2-phenylethyl)- amino]-l-piperidinylcarbonyl}benzimidazole hydrochloride 116. 4-(3-Phenyl-l-pyrrolidinyl)-1-[4-(1,2,4- triazol-1-yl)piperidine hydrochloride 117. 4-(3-Phenyl-l-pyrrolidinyl)-1-(3,5-dimethyl-4- propionylaminobenzoyl)piperidine hydrochloride 118. 4-(3-Phenyl-3-hydroxy-l-piperidinyl)-l-[4- (1,2,4-triazol-l-yl)benzoyl]piperidine hydrochloride 119. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(5- methyl-6-amino-3-pyridyl)carbonylpiperidine dihydrochloride 120. 4-[N-methyl-N-(2-phenylethyl)amino]-l-(5- methyl-6-propionylamino-3-pyridyl)carbonylpiperidine dihydrochloride 121. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(2- aminoacetyl)piperidine dihydrochloride 122. 4-[N-methyl-N-(2-phenylethyl) mino]-l-(2- dimethylaminoacetyl)piperidine dihydrochloride 123. 4-[N-methyl-N-(2-phenylethyl)amino]-1-(2- methylaminoacetyl)piperidine dihydrochloride 124. 4-[N-methyl-N-(2,3-dihydro-lH-inden-2- yl)amino]-l-acetylpiperidine hydrochloride 125. 4-[N-methyl-N-(2,3-dihydro-lH-inden-2- yl)amino]-1-[4-(1,2,4-triazol-1-yl)benzoyl]piperidine hydrochloride 126. 2-{4-[N-methyl-N-(2-phenylethyl)amino]-1- piperidinylcarbonyl}indole 127. 2-{4-[N-methyl-N-(2-phenylethyl) mino]-l- piperidinylcarbonyl}benzimidazole 128. 4-[N-methyl-N-(2-phenylethyl)amino]-1-[4-(4- hydroxyphenyl)benzoyl]piperidine 129. 4-[N-methyl-N-(2-phenylethyl)amino]-l- formylpiperidine hydrochloride 130. 4-[N-methyl-N-(2-phenylethyl)amino]-1- (benzothiazol-2-yl)carbonylpiperidine hydrochloride The results of the pharmacological test are shown in Table 12. (To be continued) (To be continued) Change in blood flow Doεe amount

Claims: CLAIMS 1. A piperidine derivative or salt thereof represented by the general formula (1) : wherein, R is a group of the formula: (wherein, m is an integer of 1 to 3; R 3 is a nitro group; a lower alkyl group; a halogen atom; a cyano group; a lower alkanoyl group; an aminocarbonyl group which may have 1 to 2 substi¬ tuents selected from the group consisting of a lower alkyl group and a phenyl group; a lower alkoxycarbonyl group; a carboxy group, a lower alkoxy group; a hydroxyl group; a hydroxyamino group; a lower alkylthio-lower alkyl group; a lower alkylsulfonyl-lower alkyl group; a hydroxy group εubεtituted-lower alkyl group; a lower alkenyl group; a lower alkoxy-carbonyl group substituted-lower alkenyl group; a phenyl group which may have subεtituent(ε) , on the phenyl ring, selected from the group consisting of a hydroxy group, a phenyl- lower alkoxy group, a lower alkanoyloxy group, a nitro group, an amino group which may have lower alkanoyl group(s), as subεtituent(s) , a lower alkyl group and a lower alkoxy group; an amino-lower alkoxy group which may have lower alkyl group(s) as substituent(ε); a ■ morpholinyl group subεtituted-lower alkoxy group; 1,2,4-triazolyl group which may have oxo group(s) as substituent(s) on the 1,2,4-triazole ring; a 1,2,3,4- tetrazolyl group; an imidazolyl group which may have 1 to 2 subεtituent(ε) selected from the group consisting of a phenyl group and a lower alkyl group on the imidazole ring; a pyrazolyl group which may have lower alkyl group(s) as substituent(s) on the pyrazole ring; a pyridyl group; a pyrrolyl group; a pyrrolidinyl group which may have oxo group(s) as substituent(s) on the pyrrolidine ring; a piperidinyl group which may have oxo group(s) as substituent(ε) on the piperidine ring; a benzimidazolyl group; an imidazolidinyl group which may have oxo group(s) as εubεtituent(s) on the imidazolidine ring; a 2-oxazolinyl group; a 1,2,4- triazolyl-lower alkyl group; a phenoxy group; a phenyl-lower alkoxy group; a lower alkanoyloxy group; a phenyl-lower alkoxycarbonyl group; an amino-lower alkyl group which may have, subεtituent(s) selected from the group consiεting of a lower alkyl group and a lower alkanoyl group; a group of the formula: ._ A (wherein, R* and R 5 are each the same or different, and are each a hydrogen atom, a lower alkyl group, a lower alkanoyl group, a lower alkanoyl group having 1 to 3 halogen atoms, a benzoyl group, a pyridylcarbonyl group, a lower alkenyl-carbonyl group, an anilinothiocarbonyl group, an aminothio-carbonyl group which may have lower alkyl group(s) as substituent(s) or an aminocarbonyl group which may have 1 to 2 substituents selected from the group consiεting of a lower alkyl group, a phenyl group and a lower alkenyl group)); a lower alkanoyl group having aε εubsti- tuent(s), hydroxyl group(s) or amino group(ε) which may have lower alkyl group(ε) as substituent(s) ; a pyridyl¬ carbonyl group which may have as substituent(s), on the pyridine ring, selected from the group consiεting of a nitro group, an amino group which may have lower alkanoyl group(s) as subεtituent(ε) , a halogen atom, a lower alkyl group, a pyrrolyl group, a lower alkylthio group, a lower alkanoyl group, a hydroxyl group, an aminocarbonyl group which may have lower alkyl group(ε) as substituent(s) , a lower alkoxycarbonyl group, a hydroxyl group εubεtituted-lower alkyl group, a phenyl group and a 1,2,4-triazolyl group; a 1,2,4-triazolyl- lower alkanoyl group; a furoyl group which haε substi- tuentε, on the furan ring, selected from the group consiεting of a nitro group, a hydroxyl group substituted-lower alkyl group, a lower alkanoyl group and an amino group which may have lower alkanoyl group(ε) aε substituent(s) ; a thienylcarbonyl group which may have substituent(s) , on the thiophene ring, selected from the group consiεting of a nitro group, a lower alkyl group, a halogen atom and an amino group which may have lower alkanoyl group(ε) aε substi- tuent(ε); a fluorenylcarbonyl group which may have εubεtituent(ε) , on the fluorene ring, εelected from the group conεiεting of an oxo group and a nitro group; or a group of the formula: (wherein, Z is a group of the formula: -CH 2 - or -NH- or a εulfur atom; Y and W are each a group of the formula: =CH- or a nitrogen atom; and the dotted line in the bonding of the formula: W iε a single bond or double A bond; and the group of the formula: may have 1 to 4 substituents selected from the group consiεting of an oxo group, a lower alkyl group, a lower alkoxy group, a hydroxyl group, a lower alkylthio group, a halogen atom, a nitro group and an amino group); R 1 is a hydrogen atom or a lower alkyl group which may have hydroxyl group as substituents; R 2 is a phenyl-lower alkyl group which may have as subεtituents, on the phenyl ring, selected from the group consisting of a lower alkoxy group, a halogen atom, a hydroxyl group, a nitro group, a lower alkyl group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkoxycarbonyl group, a carbamoyl group, a carboxy group, an amino-lower alkoxy group which may have lower alkyl group(s) as substituent(ε) , a carboxy group substituted-lower alkoxy group and an amino group which may have aε substituent(s) selected from the group consisting of a lower alkanoyl group, a lower alkoxy¬ carbonyl group, and aminocarbonyl group which may have lower alkyl group(s) aε εubstituent(s) ; further a phenyl-lower alkyl group which may have a lower alkoxy-carbonyl group or a hydroxyl group substituted-lower alkyl group as a substituent in the lower alkyl moiety; a phenoxy-lower alkyl group which may have, on the phenyl ring, substituent(s) selected from the group consiεting of a lower alkoxy group, a lower alkyl group, a halogen atom, a nitro group, an amino group which may have lower alkanoyl group(ε) aε εubstituent(s) , and a hydroxyl group, a pyridyl-lower alkyl group which may have lower alkyl group(ε) aε εubεtituent(ε) on the pyridine ring, a thienyl-lower alkyl group; a furyl-lower alkyl group, a group of the formula : (wherein B is a lower alkylene group, R 27 and R 28 are each the same or different, and are each a hydrogen atom, a lower alkyl group, a phenyl group, a lower alkanoyl group or a benzoyl group), a phthalimide substituted-lower alkyl group, a cycloalkyl-lower alkyl group, a phenyl-lower alkenyl group, a cycloalkyl group having phenyl group(s) as substituent(s) , or a 2,3-dihydro-lH-indenyl group which may have εubεtituent(ε) , on the 2,3-dihydro-lH-indene ring, εelected from the group conεiεting of a lower alkoxy a hydroxyl group, a nitro group, an amino group which may have lower alkanoyl group(s) as subεti¬ tuent(ε) ; further, R 1 and R 2 and the adjacent nitrogen atom being bonded thereto may form a pyrrolidine ring, a piperidine ring, a morpholine ring or a 1,2,3,4- tetrahydroisoquinoline ring, said heterocyclic group has subεtituent(ε) εelected from the group consisting of a hydroxyl group, a lower alkoxy group and a phenyl group; provided that, when m is 1, then R3 should not be an amino group; further, when m is 2 and either one of R 3 is an amino group, then another R 3 should be not be a halogen atom, a lower alkyl group, a lower alkoxy group, a hydroxyl group, a nitro group, an amino group, mono- or di-lower alkyl substituted-amino group. 2. A piperidine derivative or salt thereof represented by the general formula (1 ): wherein, R iε a benzoyl group or a lower alkanoyl group; R 1 iε the same as defined in Claim 1; and R 2AA is a thienyl-lower alkyl group, a phenyl- lower alkyl group having a lower alkylthio group as substituents in the phenyl ring, a 2,3-dihydro-lH- indenyl group which may have substituent, in the 2,3- dihydro-lH-indene ring, selected from the group consisting of a lower alkoxy group, a hydroxyl group, a nitro group, an amino group which may have lower alkanoyl group(s) as substituent(s) ; further, R 1 and R 2 ** and the adjacent nitrogen atom being bonded thereto may form a pyrrolidine ring, a piperidine ring, a morpholine ring or 1,2,3,4- tetrahydroisoquinoline ring, said heterocyclic ring having subεtituent(ε) εelected from the group conεiεting of a hydroxyl group, a lower alkoxy group and a phenyl group. 3. A piperidine derivative or salt thereof represented by the general formula (1 BB ): 00 ) wherein, X is an oxygen atom or a sulfur atom; R 6 and R 7 are each the same or different, and are each a hydrogen atom, a lower alkyl group or a phenyl group which may have as subεtituentε, in the phenyl ring, εelected from the group conεiεting of a lower alkoxy group, a halogen atom and a nitro group; R 1 iε the εame aε defined above; and R 2BB iε a phenyl-Ci-C-, alkyl group. 4. The piperidine derivative or salt thereof according to Claim 1, wherein R is a group of the formula: wherein R 3 and m are the same as defined above. 5. The piperidine derivative or salt thereof according to Claim 1, wherein R iε a lower alkanoyl group having, as subεituent(ε ) , hydroxyl group(ε) or amino group(s) which may have lower alkyl group(s) as the subεtituent(ε ) ; or 1,2,4-triazolyl-lower alkanoyl group. 6. The piperidine derivative or salt thereof according to Claim 1, wherein R is a pyridylcarbonyl group which may have as the substituen (s) selected from the group consisting of a nitro group, an amino group which may have lower alkanoyl group(s) as the substituent(s) , a halogen atom, a lower alkyl group, a pyrrolyl group, a lower alkylthio group, a lower alkanoyl group, a hydroxyl group, an aminocarbonyl group which may have lower alkyl group(s) as the substituent(s) , a lower alkoxycarbonyl group, a hydroxyl group(s)-substituted lower alkyl group, a phenyl group and a 1,2,4-triazolyl group, on the pyridine ring. 7. The piperidine derivative or salt thereof according to Claim 1, wherein R is a furoyl group having substituent(s), on the furan ring, selected from the group consisting of a nitro group, a hydroxyl group(s)- substituted lower alkyl group, a lower alkanoyl group and an amino group which may have lower alkanoyl group(ε) aε substituent(ε) ; a thienylcarbonyl group which may have substituent(ε), on the thiophene ring, εelected from the group consisting of a nitro group, a lower alkyl group, a halogen atom and an amino group which may have lower alkanoyl group(s) aε εubεti- tuent(ε); or a fluorenyl-carbonyl group which may have subεtituent(s) , on the fluorene ring, εelected from the group conεiεting of an oxo group and a nitro group. 8. The piperidine derivative or εlat thereof according to Claim 1, wherein R iε a group of the formula: wherein W, Y, Z and the dotted line of in the bonding of the formula: W and the substituent(s) on the group of the formula: are the same aε defined above. 9. The piperidine derivative or salt thereof according to Claim 4, wherein R 3 iε a lower alkyl group, an amino-carbonyl group which may have 1 to substituentε selected from the group consisting of a lower alkyl group and a phenyl group, a phenyl group which may have substituent(s) , on the phenyl ring, selected from the group consisting of a hydroxyl group, a phenyl-lower alkoxy group, a lower alkanoyloxy group, a nitro group, an amino group which may have lower alkanoyl group(s) as substituent(ε) , a lower alkyl group and a lower alkoxy group, 1,2,4-triazolyl group which may have oxo group(s) as substituent(s) on the 1,2,4-triazole ring; R* / or a group of the formula: -N τ (wherein R 4 and R 5 are the same as defined above). 10. The piperidine derivative or salt thereof according to Claim 4, wherein R 1 is a hydrogen atom. 11. The piperidine derivative or salt thereof according to Claim 4, wherein R 1 is a lower alkyl group which may have hydroxyl group(s) as εubεtituent(ε) . 12. The piperidine derivative or salt thereof according to Claim 5, wherein R 1 is a hydrogen atom. 13. The piperidine derivative or salt thereof accoridng to Claim 5, wherein R 1 is a lower alkyl group which may have hydroxyl group(ε) aε εubεtituent(s) . 14. The piperidine derivative or salt thereof according to Claim 6, wherein R 1 is a hydrogen atom. 15. The piperidine derivative or salt thereof accoridng to Claim 6, wherein R 1 is a lower alkyl group which may have hydroxyl group(s) aε substituent(ε) . 16. The piperidine derivative or salt thereof according to Claim 7, wherein R 1 is a hydrogen atom. 17. The piperidine derivative or salt thereof accoridng to Claim 7, wherein R 1 is a lower alkyl group which may have hydroxyl group(s) aε subεtituent(s) . 18. The piperidine derivative or salt thereof according to Claim 8, wherein R 1 is a hydrogen atom. 19. The piperidine derivative or salt thereof accoridng to Claim 8, wherein R 1 is a lower alkyl group which may have hydroxyl group(s) aε εubstituent(s) . 20. The piperidine derivative or salt thereof according to Claim 9, wherein R 1 is a hydrogen atom. 21. The piperidine derivative or εalt thereof accoridng to Claim 9, wherein R 1 iε a lower alkyl group which may have hydroxyl group(s) as substituent(s) . 22. The piperidine derivative or salt thereof according to Claims 10 to 21, wherein R 2 is a phenyl- lower alkyl group which may have, on the phenyl ring, substituent(s) selected from the group consisting of a lower alkoxy group, a halogen atom, a hydroxyl group, a nitro group, a lower alkyl group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkoxy¬ carbonyl group, a carbamoyl group, a carboxy group, an amino-lower alkoxy group which may have lower alkyl group(s) as substituent(ε), a carboxy group-substituted lower alkoxy group and an amino group which may have subεtituent(s) selected from the group consisting of a lower alkanoyl group, a lower alkoxycarbonyl group or an aminocarbonyl group which may each have lower alkyl group(s) aε εubεtituent(ε) ; εaid phenyl-lower alkyl group may have lower alkoxycarbonyl group(ε) or hydroxyl group-substituted lower alkyl group(s) aε εubεtituent(ε) in the lower alkyl moiety. 23. The piperidine derivative or εalt thereof according to Claimε 10 to 21, wherein R 2 iε a phenoxy- lower alkyl group which may have, on the phenyl ring, εubstituent(s) selected from the group consisting of a lower alkoxy group, a lower alkyl grouop, a halogen atom, a nitro group, an amino group which may have lower alkanoyl group(s) as substituent(s) , and a hydroxyl group. 24. The piperidine derivative or salt thereof according to Claimε 10 to 21, wherein R 2 is a pyridyl- lower alkyl group which may have lower alkyl group(s) as subεtituent(s) on the pyridine ring, or a thienyl-lower alkyl group. 25. The piperidine derivative or εalt thereof according to Claims 10 to 21, wherein R 2 is a 2,3- dihydro-lH-indenyl group which may have, on the 2,3-dihydro-lH-indene ring, εubεtituent(ε) εelected from the group conεiεting of a lower alkoxy group, a hydroxyl group, a nitro group, an amino group which may have lower alkanoyl group(s) as substituent(s) ; a furyl-lower alkyl group; a group of the formula: >27 (wherein B, R 27 and R 28 are the same as defined above); a phthalimido-substituted lower alkyl group; a cycloalkyl-lower alkyl group; a phenyl-lower alkenyl group or a cycloalkyl group having phenyl group(s) aε εubεtituent(ε) . 26. The piperidine derivative or salt thereof according to Claims 4 to 8, wherein R 1 and R 2 together with the adjacent nitrogen atom being bonded thereto may form a pyrrolidine ring, a piperidine ring, a morpholine ring or a 1,2,3,4-tetrahydro-isoquinoline ring; further said heterocyclic group having, substi¬ tuent(s) selected from the group conεisting of a hydroxyl group, a lower alkoxy group and a phenyl group, on the heterocyclic ring. 27. The piperidine derivative or salt thereof according to Claim 8, wherein a group of the formula: is an indolinyl group or a benzo-l,2,3-triazolyl group, 28. The piperidine derivative or salt thereof according to Claim 8, wherein a group of the formula: iε an indolyl group, a benzimidazolyl group, a benzo- thiazolyl group, a 2,3-dihydrobenzimidazolyl group or an isoindolinyl group. 29. The piperidine derivative or εalt thereof according to Claim 2, wherein R* 4 is a benzoyl group; R 1 and R 2 ^ together with the nitrogen atom being bonded thereto may form a pyrrolidine ring, a piperidine ring, a morpholine ring or a 1,2,3,4-tetrahydroisoquinoline ring, further εaid heterocyclic group having, on the heterocyclic ring, εubεtituent(ε) selected from the group consiεting of a hydroxyl group, a lower alkoxy group and a phenyl group. 30. The piperidine derivative or εalt thereof according to Claim 2, wherein R ω is a benzoyl group; and R 2 ** iε a thienyl-lower alkyl group; a phenyl-lower alkyl group having lower alkylthio group(ε) aε εubstituent(s); or a 2,3-dihydro-lH-indenyl group which may have substi¬ tuent(s) selected from the group consiεting of a lower alkoxy group, a hydroxyl group, a nitro group, an amino group which may have lower alkanoyl group(ε) aε subεtituent(s) , on the 2,3-dihydro-lH-indene ring. 31. The piperidine derivative or εalt thereof according to Claim 2, wherein R M iε a lower alkanoyl group; and R 2 ** iε a thienyl-lower alkyl group or a phenyl-lower alkyl group having lower alkylthio group(s) as substituent(s) on the phenyl ring. 32. The piperidine derivative or salt thereof according to Claim 2, wherein R ω is a lower alkanoyl group; and R 2AA is a 2,3-dihydro-lH-indenyl group which may have, on the 2,3-dihydro-lH-indene ring, subεti- tuent(ε) selected from the group consiεting of a lower alkoxy group, a hydroxyl group, a nitro group, an amino group which may have lower alkanoyl groupε(ε) as εubstituent(s) ; further R 1 and R 2 ^ together with the adjacent nitrogen atom being bonded thereto may form a pyrrolidine ring, a piperidine ring, a morpholine ring or a 1,2,3,4-tetrahydroisoquinoline ring, said hetero¬ cyclic group having subεtituent(ε) εelected from the group conεiεting of a hydroxyl group, a lower alkoxy group and a phenyl group, on the heterocyclic ring. 33. 4-[N-Methyl-N-(2-phenylethyl)amino]-1-(3- methyl-4-propionylaminobenzoyl]piperidine. 34. 4-[N-Methyl-N-(2-phenylethyl)amino]-1-(3,5- dimethyl-4-propionylaminobenzoyl)piperidine. 35. 4-{N-Methyl-N-[2-(2-thienyl)ethyl]amino}-1- (3-methyloxindol-5-yl)carbonylpiperidine. 36. 4-[N-Methyl-N-(2-phenylethyl)amino]-1-(5- propionylaminopyridin-2-yl)carbonylpiperidine. 37. 4-[N-Methyl-N-(2-phenylethyl)amino]-1-[4-(4- hydroxyphenyl)benzoyl]piperidine. 38. 4-[N-Methyl-N-(2-phenylethyl)amino]-1-[3- amino-4-(4-hydroxyphenyl)benzoyl]piperidine. 39. 4-[N-Methyl-N-(2-phenoxyethyl)amino]-1-[4- (4-hydroxyphenyl)benzoyl]piperidine. 40. 4-[N-Methyl-N-(2-phenylethyl)amino]-1-(4- methyl-benzo-1,2,3-triazol-6-yl)carbonypiperidine. 41. 4-[N-Methy1-N-(2-phenylethyl)amino]-1-(4- ethylaminocarbonylbenzoyl)piperidine. 42-a) Proceεs for preparing piperidine derivative or salt thereof represented by the general formula (la): wherein, R 1 and R 2 are the εame aε defined above; and Ra is a group of the formula: (wherein, R 3 and are the same as defined above), a lower alkanoyl group which may have hydroxyl group or amino group which may have lower alkyl group(ε) aε εubεtituent(ε) ; a lower alkanoyl group having 1 to 3 halogen atoms, a lower alkoxycarbonyl group, a pyridyl¬ carbonyl group which may have substituent(ε) , on the pyridine ring, εelected from the group conεisting of a nitro group, an amino group which may have lower alkanoyl group(s) aε εubεtituent(ε) , a halogen atom, a lower alkyl group, a pyrrolyl group, a lower alkylthio group, a lower alkanoyl group, a hydroxyl group, an aminocarbonyl group which may have lower alkyl group(ε) aε εubεtituent(ε), a lower alkoxycarbonyl group, a hydroxyl group εubstituted-lower alkyl group, a phenyl group and a 1,2,4-triazolyl group; a 1,2,4-triazolyl- lower alkanoyl group; a furoyl group which may have substituent(s) , on the furyl ring, selected from the group consisting of a nitro group, a hydroxyl group substituted-lower alkyl group, a lower alkanoyl group and an amino group which may have lower alkanoyl group(s) as substituent(s) ; a thienylcarbonyl group which may have substituent(s) , on the thienyl ring, selected from the group consisting of a nitro group, a lower alkyl group, a halogen atom and an amino group which may have lower alkanoyl group(s) as substi¬ tuent(s); a fluorenylcarbonyl group which may have substituent(s) , on the fluorene ring, selected from the group consisting of an oxo group and a nitro group; or group of the formula: (wherein, Z is a group of the formula: -CH 2 - or -NH- or a sulfur atom; Y and are each a group of the formula: =CH- or a nitrogen atom; and the dotted line in the bonding of the formula: —W is a single bond or a double bond; il and the substituents which are bonded on the group of the formula: are the same as defined above), by reacting a carboxylic acid derivative represented by the general formula (2) : Ra-OH (2) (wherein Ra is the same as defined above), or a carboxylic acid derivative obtained by activating the carboxyl group of said derivative, with an amine compound represented by the general formula (3) : (wherein R 1 and R 2 are the same as defined above), or an amine compound obtained by activating the amino group of thereof. 42-b) Process for preparing a piperidine derivative represented by the general formula (lm): (wherein R 1 , R 1 , R 6 , and X are the same as defined above; and R 7 a is a lower alkyl group), by reacting a piperidine derivative repre¬ sented by the general formula (3) : (wherein R 1 and R 2 are the same as defined above), with a compound represented by the general formula (4) : R 6 -NCX (4) (wherein R 6 and X are the same as defined above), to obtain a piperidine derivative represented by the general formula (lb): (wherein R 1 , R 2 , R 6 and X are the same as defined above), then thus obtained piperidine derivative of the general formula (lb) is reacted with a compound of the general formula (14): R 7 a-X : (14) (wherein R 7 a and X 1 are the same as defined above) to obtain the desired piperidine derivative of the general formula (lm) . 42-c) Process for preparing a piperidine derivative or salt thereof represented by the general formula (1) : (wherein R, R 1 and R 2 are the same aε defined above), by reacting a compound repreεented by the general formula (5): 0 (5) (wherein R is the same as defined above), with an amine compound represented by the general formula (6) : R 1 / HN (6) R 2 (wherein R 1 and R 2 are the same as defined above). 42-d) Process for preparing a piperidine derivative represented by the general formula (Id): >la wherein R is the same as defined above; R 2a is a hydrogen atom; a lower alkyl group which may have hydroxyl group(s) as subεtituent(s); a phenyl-lower alkyl group which may have subεtituent(s) , on the phenyl ring, εelected from the group conεiεting of a lower alkoxy group, a halogen atom, a hydroxyl group, a nitro group, a lower alkyl group, a lower alkylthio group,a lower alkylsulfinyl group, a lower alkoxycarbonyl group, a carbamoyl group, a carboxyl group, an amino-lower alkoxy group which may have lower alkyl group(s) aε substituent(s) , a carboxy-substituted lower alkoxy group and an amino group which may have, as subεtituent(s) , lower alkanoyl group(s), lower alkoxy- carbonyl group(s), or aminocarbonyl group(s) which may each have lower alkyl group(ε) aε εubεtituent(ε) , which phenyl-lower alkyl group may have lower alkoxycarbonyl group(ε) or hydroxyl-substituted lower alkyl group(s) as substituent(s) in the lower alkyl moiety; a phenoxy-* lower alkyl group which may have, on the phenyl ring, subεtituent(ε) εelected from the group consisting of a lower alkoxy group, a lower alkyl group, a halogen atom, a nitro group, a hydroxyl group and an amino group which may have lower alkanoyl group(s) as substituent(s) ; a pyridyl-lower alkyl group which may have lower alkyl group(s) as substituent(s) on the pyridine ring; a thienyl-lower alkyl group; a furyl-lower alkyl group; a group of the formula: R 27 / -B-N R 28 (wherein, B, R 27 and R 28 are the same as defined above); a phthalimido-substituted lower alkyl group; a cycloalkyl-lόwer alkyl group; a phenyl-lower alkenyl group; a cycloalkyl group which may have a phenyl group as a substituent; or a 2,3-dihydro-lH-indenyl group which may have εubεtituent(ε) , on the 2,3-dihydro-lH- indene ring, selected from the group consiεting of a lower alkoxy group, a hydroxyl group, a nitro group and an amino group which may have lower alkanoyl group(s); R la is the εame as defined in R 2a , excluding a hydrogen atom; and X 1 is a hydrogen atom, a lower alkane- εulfonyloxy group, an arylεulfonyloxy group or an aralkylsulfonyloxy group, provided that, when R 2 * is the same as defined above, except a hydrogen atom and a lower alkyl group which may have hydroxyl group(s) as substituent(s) , then R la should be a lower alkyl group which may have hydroxyl group(s) aε εubstituent(s) ; further, when R 2a is a hydrogen atom or a lower alkyl group which may have hydroxyl group(s) as substi¬ tuent(ε), then R la εhould be the same as defined above, except a lower alkyl group which may have hydroxyl group(s) as substituent(s)] . by reacting a compound of the general formula (lc): R-N \-NHR 2a (lc) (wherein R and R 2 are the same as defined above), with a compound of the general formula (7) : R la -X : (7) (wherein R l and X : are the same as defined above). 42-e) Procesε for preparing a piperidine derivative repreεented by the general formula (le): (wherein R, and R 2a are the same as defined above; and R lc is the same aε defined in R 23 , excluding a hydrogen atom and 2,3-dihydro-lH-indenyl group which may have, on the 2,3-dihydro-lH-indene ring, substituent(s) selected from the group consisting of a lower alkoxy group, a hydroxyl group, a nitro group, an amino group which may have lower alkanoyl group(s) as substituent(ε) ; a phenyl-lower alkyl group which may have, on the phenyl ring, substituent(ε) εelected from the group consisting of a lower alkoxy group, a halogen atom, a hydroxyl group, a nitro group, a lower alkyl group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkoxycarbonyl group, a carbamoyl group, a carboxy group, an amino-lower alkoxy group which may have lower alkyl group(s) as subεtituent(s) , a carboxy group-substituted lower alkoxy group and an amino group which may have substituent(ε) selected from the group consiεting of a lower alkanoyl group, a lower alkoxy¬ carbonyl group and aminocarbonyl group(ε) which may each have lower alkyl group(ε) as substituent(ε) , which phenyl-lower alkyl group has lower alkoxycarbonyl group(s) or hydroxyl group-substituted lower alkyl group(s) aε εubεtituent(ε) in the alkyl moiety; and a cycloalkyl group which may have phenyl group(ε) aε εubstituent(s) ) ; by reacting a compound of the general formula (lc): R-N V- NHR 28 ( lc ) (wherein R and R 2s are the εame aε defined above), with a compound repreεented by the general formula (8) : R lb -CHO (8) (wherein R lb iε a phenyl group which may have, on the phenyl ring, εubεtituent(ε) selected from the group consiεting of a lower alkoxy group, a halogen atom, a hydroxyl group, a nitro group, a lower alkyl group, a lower alkylthio group, a lower alkylεulfinyl group, a lower alkoxycarbonyl group, a carbamoyl group, a carboxyl group, an amino-lower alkoxy group which may have lower alkyl group(ε) aε substituent(s) , a carboxy- εubεtituted lower alkoxy group and an amino group which may have, as subεtituent(ε) , lower alkanoyl group(ε), lower alkoxycarbonyl group(ε) or aminocarbonyl group(ε); which may each have lower alkyl group(ε) aε εubsti¬ tuent(s); a pyridyl group which may have lower alkyl group(s) as subεtituent(s) on the pyridine ring; a thienyl group; a furyl group; a phthalimido group; a cycloalkyl group; or the εubεtituentε the εame aε defined in R 2a excluding, a hydrogen atom, 2,3-dihydro- lH-indenyl group which may have, on the 2,3-dihydro-lH- indene ring, εubstituent(s) εelected from the group conεisting of a lower alkoxy group, a hydroxyl group, a nitro group ans an amino group which may have lower alkanoyl group(s) as subεtituent(ε) , a phenyl-lower alkyl group which may have, on the phenyl ring, substituent(ε) selected from the group consisting of a lower alkoxy group, a halogen atom, a hydroxyl group, a nitro group, a lower alkyl group a lower alkylthio group, a lower alkylsulfinyl group, a lower alkoxy¬ carbonyl group, a carbamoyl group, a carboxy group, an amino-lower alkoxy group which may have lower alkyl group(s) as subεtituent(s) , a carboxy group-εubstituted lower alkoxy group and an amino group which may have substituent(s) selected from the group consisting of a lower alkanoyl group, a lower alkoxycarbonyl group and aminocarbonyl group(s) which may each have lower alkyl group(s) as substituent(s) , which phenyl-lower alkyl group has lower alkoxycarbonyl group(s) or hydroxyl group-substituted lower alkyl group(s) as substituent(s) in the lower alkyl moiety, and cycloalkyl group which may have phenyl group(s) as substituent(ε)) . 42-f) Proceεε for preparing a piperidine derivative repreεented by the general formula (If): ,R 8 (wherein R and R 2a are the same as defined above; and R 8 and R 9 independently repreεent a hydrogen atom or a lower alkyl group provided that, in compound (If), R 23 iε other than a hydrogen atom or a lower alkyl group which may have hydroxyl group(s) as substituent(s)) , by reacting a piperidine derivative repre¬ sented by the general formula (lc): (wherein R and R 2a are the same as defined above), with a compound of the general formula (9) : R 8 (wherein R 8 and R 9 are the same as defined above). 42-g) Process for preparing a piperidine derivative represented by the general formula (IB): (IB) wherein R 1 and R 2 are the same aε defined above; and R b iε a group of the formula: (wherein R 3 and m are the εame aε defined above); a lower alkyl group which may have hydroxyl group(s) or amino group(s) which may each have lower alkyl group(ε); a lower alkyl group having 1 to 3 halogen atomε; a pyridyl group which may have, on the pyridine ring, substituent(s) selected from the group consiεting of a nitro group, an amino group which may have lower alkanoyl group(s) as substituent(s) , a halogen atom, a lower alkyl group, a pyrrolyl group, a lower alkylthio group, a lower alkanoyl group, a hydroxyl group, an aminocarbonyl group which may have lower alkyl group(s) as subεtituent(ε) , a lower alkoxycarbonyl group, a hydroxyl group-substituted lower alkyl group, a phenyl group and a 1,2,4-triazolyl group; a 1,2,4-triazolyl- lower alkyl group; a furyl group which may have, on the furan ring, subεtituent(s) εelected from the group conεisting of a nitro group, a hydroxyl group- εubεtituted lower alkyl group, a lower alkanoyl group and an amino group which may have lower alkanoyl group(s) as subεtituent(s) ; a thienyl group which may have, on the thiophene ring, εubstituent(s) selected from the group conεiεting of a nitro group, a lower alkyl group, a halogen atom and an amino group which may have lower alkanoyl group(ε) as substituent(ε) ; a fluorenyl group which may have, on the fluorene ring, εubεtituent(ε) εelected from the group conεisting of an oxo group and a nitro group; or a group of the formula: (wherein, Y, , Z, the dotted line in the bond of —W A and the substituent(s) in the group of the formul : are the εame as defined above); by reacting a compound of the formula (33): Rb-CHO (33) (wherein Rb is defined above), with a piperidine compound of the formula (3) (wherein R 1 and R 2 are the same as defined above). 43. A peripheral vaεodilating agent containing, aε the active ingredient, a piperidine derivative or εalt thereof aε claimed in Claim 1. 44. A peripheral vaεodilating agent containing, aε the active ingredient, a piperidine derivative or εalt thereof aε claimed in Claim 2. 45. A peripheral vaεodilating agent containing, aε the active ingredient, a piperidine derivative or salt thereof as claimed in Claim 3. 46. Method for use of peripheral vasodilating agent containing, as the active ingredient, a piperidine derivative or salt thereof represented by the general formula (1) : wherein, R is a group of the formula: (wherein, m is an integer of 1 to 3; R 3 iε a hydrogen atom, a nitro group; a lower alkyl group; a halogen atom; a cyano group; a lower alkanoyl group; an aminocarbonyl group which may have 1 to 2 εubεtituentε εelected from the group conεiεting of a lower alkyl group and a phenyl group; a lower alkoxycarbonyl group; a carboxy group, a lower alkoxy group; a hydroxyl group; a hydroxyamino group; a lower alkylthio-lower alkyl group; a lower alkylsulfonyl-lower alkyl group; a hydroxyl group substituted-lower alkyl group; a lower alkenyl group; a lower alkoxycarbonyl group subεtituted-lower alkenyl group; a phenyl group which may have εubεtituent(ε) , on the phenyl ring, εelected from the group consisting of a hydroxy group, a phenyl-lower alkoxy group, a lower alkanoyloxy group, a nitro group, an amino group which may have lower alkanoyl group(s) as substituent(s) , a lower alkyl group and a lower alkoxy group; an amino-lower alkoxy group which may have lower alkyl group(s) as substituent(s) ; a morpholinyl group substituted-lower alkoxy group; 1,2,4-triazolyl group which may have oxo group(s) as substituent(s) on the 1,2,4-triazole ring; a 1,2,3,4- tetrazolyl group; an imidazolyl group which may have 1 to 2 substituents, on the imidazole ring, selected from the group consisting of a phenyl group and a lower alkyl group; a pyrazolyl group which may have lower alkyl group(s) as substituent(s) on the pyrazole ring; a pyridyl group; a pyrrolyl group; a pyrrolidinyl group which may have oxo group(s) as substituent(s) on the pyrrolidine ring; a piperidinyl group which may have oxo group(s) aε subεtituent(ε) on the piperidine ring; a benzimidazolyl group; an imidazolidinyl group which may have oxo group(ε) aε εubstituent(s) on the imidazolidine ring; a 2-oxazolinyl group; a 1,2,4-triazolyl-lower alkyl group; a phenoxy group; a phenyl-lower alkoxy group; a lower alkanoyloxy group; a phenyl-lower alkoxy¬ carbonyl group; an amino-lower alkyl group which may have, substituent(s) selected from the group consiεting of a lower alkyl group and a lower alkanoyl group; a group of the formula: -N (wherein, R A and R 5 are each the εame or different, and are each a hydrogen atom, a lower alkyl group, a lower alkanoyl group, a lower alkanoyl group having 1 to 3 halogen atomε, a benzoyl group, a pyridylcarbonyl group, a lower alkenyl-carbonyl group, an anilinothiocarbonyl group, an aminothio-carbonyl group which may have lower alkyl group aε substi-tuent(ε) or an aminocarbonyl group which may have 1 to 2 εubεtituents selected from the group consisting of a lower alkyl group, a phenyl group and a lower alkenyl group)); a group of the formula: X R 6 » / -C-N (wherein, X is an oxygen atom or a sulfur atom; R 6 and R 7 are the same or different, and are eacha hydrogen atom, a lower alkyl group, or a phenyl group which may have εubεtituent(ε) , on the phenyl ring, εelected from the group consisting of a lower alkoxy group, a halogen atom and a nitro group), a lower alkanoyl group which may have hydroxyl group or amino group which may have lower alkyl group(ε) aε subεtituent(s) ; a lower alkanoyl group having 1 to 3 halogen atomε, a lower alkoxycarbonyl group, a pyridyl¬ carbonyl group which may have εubεtituent(s) , on the pyridine ring, selected from the group consiεting of a nitro group, an amino group which may have lower alkanoyl group(s) as substituent(s) , a halogen atom, a lower alkyl group, a pyrrolyl group, a lower alkylthio group, a lower alkanoyl group, a hydroxyl group, an aminocarbonyl group which may have lower alkyl group(s) as substituent(s) , a lower alkoxycarbonyl group, a hydroxyl group substituted-lower alkyl group, a phenyl group and a 1,2,4-triazolyl group; a 1,2,4-triazolyl- lower alkanoyl group; a furoyl group which may have substituent(s) , on the furan ring, selected from the group consiεting of a nitro group, a hydroxyl group εubεtituted-lower alkyl group, a lower alkanoyl group and an amino group which may have lower alkanoyl group(ε) aε substituent(ε) ; a thienylcarbonyl group which may have εubεtituent(ε) , on the thiophene ring, εelected from the group conεiεting of a nitro group, a lower alkyl group, a halogen atom and an amino group which may have lower alkanoyl group(ε) aε substi¬ tuent(s); a fluorenylcarbonyl group which may have subεtituent(ε) , on the fluorene ring, selected from the group consisting of an oxo group and a nitro group; or a group of the formula: (wherein, Z is a group of the formula: -CH 2 - or -NH- or a sulfur atom; Y and are each a group of the formula: =CH- or a nitrogen atom; and the dotted line in the bonding of the formula: —W ; ι iε a εingle bond or a double bond); and a group of the formula: may have 1 to 4 subεtituent(s) εelected from the group conεiεting of an oxo group, a lower alkyl group, a lower alkoxy group, a hydroxyl group, a lower alkylthio group, a halogen atom, a nitro group and an amino group; R 1 iε a hydrogen atom or a lower alkyl group which may have hydroxyl group(ε) aε substituent(s) ; R 2 is a phenyl-lower alkyl group which may have as εubεtituent(ε) , on the phenyl ring, εelected from the group conεiεting of a lower alkoxy a halogen atom, a hydroxyl group, a nitro group, a lower alkyl group, a lower alkylthio group, a lower alkyl- εulfinyl group, a lower alkoxycarbonyl group, a carbamoyl group, a carboxy group, an amino-lower alkoxy group which may have lower alkyl group(s) as substi¬ tuent(s), a carboxy group substituted-lower alkoxy group and an amino group which may have as εubεtituent(ε) selected from the group consisting of a lower alkanoyl group, a lower alkoxycarbonyl group, and aminocarbonyl group which may have lower alkyl group as subεtituent(s) ; further, a phenyl-lower alkyl group which may have a lower alkoxy-carbonyl group or a hydroxyl group εubεtituted-lower alkyl group aε εubεtituent(ε) in the lower alkyl moiety; a phenoxy-lower alkyl group which may have, on the phenyl ring, εubstituent(s) selected from the group consisting of a lower alkoxy group, a lower alkyl group, a halogen atom, a nitro group, an amino group which may have a lower alkanoyl group as subεtituent(s) , and a hydroxyl group, a pyridyl-lower alkyl group which may have lower alkyl group(ε) as substituent(s) on the pyridine ring, a thienyl-lower alkyl group; a furyl-lower alkyl group, a group of the formula: R 27 -B-N / (wherein, B iε a lower alkylene group; R 27 and R 28 R 28 are each the εame or different, and are each a hydrogen atom, a lower alkyl group, a phenyl group, a lower alkanoyl group or a benzoyl group), a phthalimide substituted-lower alkyl group, a cycloalkyl-lower alkyl group, a phenyl-lower alkenyl group, a cycloalkyl group which may have phenyl group(s) as substituent(s) , or a 2,3-dihydro-2H-indenyl group which may have as εubεtituent(ε) , on the 2,3-dihydro- lH-indene ring, selected from the group consiεting of a lower alkoxy group, a hydroxyl group, a nitro group, an amino group which may have lower alkanoyl group aε substituentε; further, R : and R 2 and the adjacent nitrogen atom being bonded thereto may form a pyrrolidine ring, a piperidine ring, a morpholine ring or a 1,2,3,4-tetra- hydroiεoquinoline ring, said heterocyclic group which may have subεtituent(ε) εelected from the group conεiεting of a hydroxyl group, a lower alkoxy group and a phenyl group; provided that, when m is 1; and R 3 is an amino group, then R 3 should not be subεtituted at 4-position in the benzoyl group) .

Inventors: FUJIOKA TAKAFUMI, SHIMIZU HIROSHI, TABUSA FUJIO, TANAKA MICHINORI, TERAMOTO SHUJI, TOMINAGA MICHIAKI, FUJIOKA, TAKAFUMI, SHIMIZU, HIROSHI, TABUSA, FUJIO, TANAKA, MICHINORI, TERAMOTO, SHUJI, TOMINAGA, MICHIAKI
Applicants: FUJIOKA TAKAFUMI, OTSUKA PHARMA CO LTD, SHIMIZU HIROSHI, TABUSA FUJIO, TANAKA MICHINORI, TERAMOTO SHUJI, TOMINAGA MICHIAKI, FUJIOKA, TAKAFUMI, OTSUKA PHARMACEUTICAL CO., LTD., SHIMIZU, HIROSHI, TABUSA, FUJIO, TANAKA, MICHINORI, TERAMOTO, SHUJI, TOMINAGA, MICHIAKI
Application year: 1994
Main classification: C07D211
IPC codes: C07D211, C07D401, C07D405, C07D409, C07D413, C07D417, C07D521